DNA STRUCTURE-SPECIFIC RECOGNITION PROTEIN AND USES THEREFOR

Abstract: DNA structure specific recognition protein of eukaryotic origin and DNA encoding such a factor, as well as probes specific for DNA structure specific recognition protein or DNA encoding it and methods of detecting DNA structure specific recognition protein in eukaryotic cells. In particular, a mammalian cellular factor that selectively recognizes and binds DNA damaged or modified by a drug (the anticancer drug, cis-diaminedichloroplatinum (II) or cisplatin) has been identified.

Description: DNA STRUCTURE-SPECIFIC RECOGNITION PROTEIN AND USES THEREFOR Background DNA can be damaged by a variety of environmental insults, including antitumor drugs, radiation, carcinogens, mutagens and other genotoxins. Chemical changes in the component nucleotides or of DNA secondary and tertiary structure which arise from such external causes are all considered herein to be DNA modification or damage. In addition, it is recognized that certain chemical and/or structural modifications in DNA may occur naturally, and may play a role in, for example, DNA replication, expression, or the coordinate regulation of specific genes. It has been proposed that some types of DNA modification or damage arising from external sources are similar to, or even mimic, certain types of natural DNA chemical and/or structural modification. The mechanism(s) by or conditions under which DNA modification or damage occurs are presently unknown or poorly understood. It would be very helpful to have a better understanding of DNA damage, because DNA damage can lead to mutations and cancer, as well as cell death; the latter is exploited in chemo- and radio-therapeutics. A better understanding of DNA chemical and structural modifications, including DNA damage, would also be helpful in that it might serve as the basis for developing an enhanced ability to repair or otherwise modify the effects of such damage, leading in turn to improved organis al or suborganismal resistance to DNA damaging agents. Summary of the Invention The present invention relates in one aspect to a DNA damage-binding factor, referred to herein as a DNA structure-specific recognition protein or SSRP; it has previously been referred to as a DNA damage recognition protein or DRP. The SSRP has been shown to bind selectively to damaged DNA in mammalian cell extracts. In another aspect, the invention described herein relates to nucleotide sequences which encode SSRP. In still another aspect, it relates to a method of identifying SSRP in eukaryotic cells. Other aspects of the present invention relate to use of SSRP, amino acid sequences encoding SSRP and antibodies which bind to the structure-specific recognition protein described herein. Furthermore, this invention relates to methods of preventing or reducing damage to DNA that is the result of DNA processing (e.g., replication, recombination and repair) or is caused by contact with or exposure to a chemical compound, physical substance or other damaging- agent which produces a particular, recognizable type of DNA structural damage. The DNA structure-specific recognition protein of the present invention binds selectively to double-stranded (ds) DNA which has been structurally modified as a result of exposure to a chemical agent, such as a therapeutic agent administered for cancer therapy. Specifically, SSRP of the present invention binds selectively to ds DNA containing at least one 1,2-intrastrand dinucleotide adduct. SSRP has been shown to bind selectively to a damaged DNA fragment, by which is meant a ds DNA fragment which contains a 1,2-intrastrand dinucleotide adduct of a therapeutically active platinum compound, such as ciε- diamminedichloroplatinum (II) (cis-DDP or cisplatin). As a result of selective binding of the SSRP to cisplatin- damaged DNA, a (damaged DNA fragment) : (protein) complex is formed. The electrophoretic mobility of this complex is retarded, relative to the mobility of the damaged DNA fragment alone (i.e., not having SSRP bound thereto). Therefore, the complex can be electrophoretically resolved from the damaged DNA fragment alone. cis-DDP SSRP of the present invention has been shown to bind selectively to damaged ds DNA containing the 1,2- intrastrand d(GPG) and d(ApG) dinucleotide adducts formed by cis-DDP. This binding is selective in that the SSRP does not significantly bind to single-stranded (ss) DNA, or to ds DNA lacking a 1,2-intrastrand dinucleotide adduct such as the d(ApG) and d(GpG) adducts formed by cisplatin. The present invention also encompasses a generally applicable method of identifying other DNA structure- specific recognition proteins in eukaryotic cells, particularly those encoded by DNA which hybridizes to the DNA encoding the cis-DDP SSRP described and claimed herein. That is, this method can be used to identify other proteins having cis-DDP SSRP activity, encoded by DNA which comprises at least a region of sequence homologous to the cis-DDP SSRP gene. The present invention encompasses SSRPs identified by this method. Brief Description of the Drawings Figure 1 is an illustration of the nucleotide sequence of synthetic duplex oligonucleotides containing specific platinum adducts. The 22-base olignucleotides containing specific platinum adducts and designated as Top strands are shown 5' → 3' with their complementary bottom strands. Figure 2 is a graphic illustration of the sedimentation of the cellular SSRP through a sucrose density gradient. D, protein concentration (mg/mL) ; A, C, and -, sedimentation coefficient size markers (A, albumin (M- of 67 000 daltons) ; C, catalase (M_. of 232 000 daltons) ) . The hatched box indicates the sedimentation region corresponding to cis-DDP-DNA binding activity (as determined by EMSA study of the fractions) . Figure 3 is a schematic representation of the restriction endonuclease maps of phages λPtl and λPt2 showing the 5' alignment of their cDNA inserts. Figure 4 is a schematic illustration showing the relationship among human cDNA clones encoding SSRP. Figure 5 is a composite nucleotide sequence of the human gene for structure-specific recognition protein, shown together with the predicted amino acid sequence of the encoded protein. Figure 6 is a schematic illustration, prepared from the predicted amino acid sequence of the human SSRP gene showing various domains of the human structure-specific recognition protein. HMG or HMG-box; domain having a high degree of sequence homology to high mobility group 1 protein. Figure 7 is a schematic illustration showing the relationship between Drosophila melanog aster cDNA clones DM 3002 and DM 1001. Figure 8 is a composite nucleotide sequence of the D. melangaster gene for structure-specific recognition protein, shown together with the predicted amino acid sequence of the encoded protein. Figure 9 is a schematic illustration, prepared from the predicted amino acid sequences of the human and the D . melanogaster (Dmel) SSRP genes, showing various domains of the structure-specific recognition protein homologs. Figure 10 is a schematic illustration of the positions of restriction endonuclease sites in the λyPt clone. Figure 11 is the nucleotide sequence of the λyPt clone, which includes a fractional sequence for the yeast structure-specific recognition protein (ySSRP) gene. Figure 12 is the predicted amino acid sequence of fractional yeast structure-specific recognition protein (fySSRP) , encoded by λyPt. Detailed Description of the Invention The present invention is based on the discovery in extracts of eukaryotic cells of a DNA structure-specific recognition protein (SSRP) , which recognizes and selectively binds to a structural motif present in damaged DNA. SSRP was originally defined by its characteristic of selectively binding to DNA damaged by therapeutically active platinum compounds and thus it was previously referred to as a DNA damage-recognition protein (DRP) , and specifically as a cis-DDP DRP. The protein disclosed and referred to as cis-DDP DRP in U.S. Serial Nos. 07/539,906 and 07/410,981 is the same as the protein described herein as SSRP. The term "structural motif" is intended to encompass any type of nucleic acid secondary structure or tertiary structure which differs in a detectable manner from ordinary helical duplex DNA. Structural motifs can be sequence-dependent or sequence-independent. Thus, cruciform DNA, kinked DNA, overwound, partially unwound or underwound helical DNA, different helical forms of DNA (e.g., A or Z helices), junctions between different helical forms, modified bases (e.g., thymine dimers, methylated guanosine or cytosine residues) , and combinations thereof, are all examples of DNA structural motifs. See generally, W. Saenger, Principles of Nucleic Acid Structure , Springer Advanced Texts in Chemistry. C. Cantor, series ed., Springer-Verlag New York, Inc., New York (1984). Structural motifs can be .generated during the course of normal or aberrant cellular activities in which DNA participates, such as DNA replication, recombination, or repair. Certain structural motifs comprise DNA damage or lesions; others are thought to be associated with the control of cellular processes. Structural motifs generally classified as DNA damage can be produced by drugs which interact with nucleic acids to form detectable lesions such as base- or sugar-drug adducts, or intercalations. DNA damage-associated structural motifs can also be produced spontaneously, e.g., by exposure to or contact with an environmental damage-causing agent. Such an agent can be a chemical compound or a physical agent (e.g., UV radiation). Friedberg, E.C., DNA Repair . Chapter 1, W.jj. Freeman & Co., New York (1985). A DNA structural motif of particular interest comprises a 1,2-intrastrand dinucleotide adduct. This type of structural motif or lesion is known to be formed as a result of the interaction of therapeutically effective platinum compounds which are used for the treatment of cancer (e.g., cis-DDP or cisplatin) with DNA. As described more fully below, it has been suggested that the structural motif or lesion produced by therapeutically active platinum drugs interacts with the cellular machinery for DNA repair. Therefore, a factor, such as a protein, which is capable of selectively recognizing this structural motif (i.e., a platinated DNA motif comprising a region of DNA damage or a lesion, specifically a 1,2- intrastrand dinucleotide adduct of cisplatin) , is a valuable tool for developing an understanding of the mechanisms underlying susceptability and/or resistance to cancer and to particular cancer therapeutics. Accordingly, the platinated 1,2-intrastrand dinucleotide adduct DNA structural motif has been employed as a model system for the method of the invention described herein. It will be understood that the present method of identification and isolation of structure-specific recognition proteins (SSRPs) can also be used to identify and isolate SSRPs which recognize other DNA structural motifs; its utility is not confined to the 1,2-intrastrand dinucleotide adduct of a therapeutically effective platinum compound. The present invention relates to a method of identifying and isolating DNA structure specific recognition proteins (SSRPs) which bind selectively to particular DNA structural motifs present in mamalian cells as a result of spontaneous damage or environmental damage. It relates to SSRPs identified according to this method, and to antibodies reactive with these SSRPs. It relates further to DNA and RNA and to nucleic acid probes encoding SSRPs identified according to the method described herein. The method of the present invention will now be described in the context of its use to identify and characterize a DNA structure-specific recognition protein which selectively binds cisplatin-modified DNA. cis-DDP SSRP was identified and characterized in mammalian and other eukaryotic cells, as described more fully in the Examples which follow. Isolation and cloning of a human cDNA encoding SSRP of the present invention is also described herein. Other aspects of the present invention comprising the use of SSRP as well as of nucleotide sequences encoding it and antibodies reactive with it, for therapeutic, diagnostic and prophylactic purposes are also discussed below. Platinated DNA structural motifs cis-Diam inedichloroplatinum(II) (cis-DDP or cisplatin) is a clinically important antitumor drug used mainly to combat ovarian and testicular malignancies. Loehrer, P.J. and L.H. Einhorn, Ann. Intern. Med.. 100:704-713 (1984). The major cellular target for cis-DDP is generally accepted to be DNA, although it is not yet certain whether antitumor efficacy is a consequence of impaired replication or transcription. Sorenson, S.M. and A. Eastman, Cancer Res. 48:4484-4488 and 6703-6707 (1988) . Covalent coordination of the hydrolysis products of cis- DDP to the bases in DNA can lead to inhibition of DNA synthesis in vitro and in vivo and cause mutagenesis. Lee, K.W. and D.S. Martin, Jr., Inorg. Chi . Acta r 17:105- 110 (1976); Lim, M.C. and R.B. Martini, J. Inorg. Nucl. Chem. 38:119-1914 (1984); Pinto, A.L., and S.J. Lippard, Proc. Natl. Acad. Sci.. USA. 82: 4616-4619 (1985); Harder, H.C., and B. Rosenberg, Int. J. Cancer. 6:207-216 (1970); Howie, J.A. and G.R. Gale, Biochem. Pharmacol. 19:2757- 2762 (1970); Burnouf, D. et al.. Proc. Natl. Acad. Sci.. USA. 84:3758-3762 (1987). trans-Diamminedichloroplatinum(II) , the geometic isomer of cis-DDP in which the amine and chloride moieties are in mutually trans positions, is ineffective as a chemotherapeutic agent. Connors, T.A. et al.. Chem.-Biol. Interact. 5:415-424 (1972) . trans-DDP will block replication at doses equitoxic to those of cis-DDP. It has been postulated that differential repair may be responsible for the chemotherapeutic effectiveness of cis- DDP compared to trans-DDP. Ciccarelli, R.B. et al.. Biochemistry 24:7533-7540 (1985). The trans-DDP reaction products with DNA include onofunctional adducts, intrastrand cross-links, interstrand cross-links, and protein-DNA cross-links. Pinto A.L. and S.J. Lippard, Proc. Natl. Acad. Sci. USA 82:4616-4619 (1985); Eastman, A. and M.A. Barry, Biochemistry 26:3303-3307 (1987). trans-DDP cannot form intrastrand cross-links between adjacent nucleotides, and this observation has led to the suggestion that the d(GpG) and d(ApG) adducts formed uniquely by cis-DDP are responsible for its antitumor activity. Cardonna, J.P. and S. J. Lippard, Adv. chem. Ser. 209:14-16 (1983); and Pinto, A.L. and S.J. Lippard, Biochem. Biophys. Acta 780:167-180 (1985). This hypothesis is supported by the observation that most chemotherapeutically effective platinum compounds have chloride moieties in ciε positions and are believed to form a spectrum of DNA adducts similar to those of cis- DDP, i.e., 1,2-intrastrand cross-links. Lippard, S.J. et al.. Biochemistry 22:5165-5168 (1983). The chemical formulae for cis- and trans-DDP, and for several clinically related platinum compounds are as follows: cis-DDP binds to DNA in a bidentate manner, forming mainly 1,2-intrastrand d(GpG) and d(ApG) crosslinks that • kink the strand of the helix bearing the platinated adduct, and possibly concurrently form a localized single stranded region of the opposite strand which would be detectable by antinucleoside antibodies. Sherman, S.E., and S.J. Lippard, Chem. Rev.. 87:1153-1181 (1987); Rice, J.A. et at.. Proc. Natl. Acad. Sci.. USA. 85:4158-4161 (1988); Sundquist, W.I. et al.. Biochemistry. 25:1520- 1524 (1986). The 1,2- intrastrand d(GpG) adduct of cis- DDP produces a bend in the helix of DNA by 32-34° directed toward the major groove (Rice, J. A., Crothers, D.M. , Pinto, A.L. & Lippard, S.J. (1988) Proc. Natl. Acad. Sci. U.S.A. 85:4158-4161; Bellon, D.F. & Lippard, S.J. (1990) Biophys. Chem. 35: 179-188). Initially, it was thought that either this kink or the postulated local region of ss DNA opposite to the platinum adduct could comprise a recognizable structural motif. The 1,3-intrastrand d(GpTpG) adduct of cis-DDP also bends the helix by 34°, concurrently unwinding the DNA strand opposite to the adduct to a much greater degree than in the 1,2-intrastrand adducts produced by this compound. Moreover, it is not known if this bend is directed toward the major groove of the DNA helix. It is possible that the helix bend produced by this platinum adduct is more flexible than the helix kink produced by the 1,2-intrastrand adducts of cis-DDP. Bellon, S.F. & Lippard, S.J. (1990) Biophvs. Chem. 35:179-188. It should be noted that cyclobutane-type pyri idine dimers formed by UV irradiation also have been suggested to bend the DNA helix by 30°. Husain, I., Griffith, J. , & Sancar, A. (1988) Proc. Natl. Acad. Sci. U.S.A. 85:2558-2562. This bend is probably in the direction of the major groove. Pearlman, D.A. , Holbrook, S.R., Pirkle, D.H. & Kim, S. (1985) Science 227:1304-1308. The other platinum compounds illustrated above form interstrand platinated DNA adducts (e.g., trans-DDP) or monofunctional adducts (e.g., {Pt(dien)C1}C1 or {Pt(NH 3 ) 2 (N3-cytosine)>) . The above-illustrated platinum compounds were employed to investigate the nature of the structural motif produced by therapeutically active platinum compounds and selectively recognized by SSRP. It was possible to determine whether the motif recognized by the cis-DDP SSRP described below comprised a particular helix kink or bend, a local region of DNA unwinding, the platinum atom itself, or a combination of these elements. Method of identifying SSRP in cell extracts DNA modified by the antitumor drug cis-diammine- dichloroplatinum(II) (cis-DDP or cisplatin) was used to identify a factor present in crude extracts of mammalian cells which binds to cisplatin-damaged DNA. This factor, referred to as cis-DDP DNA structure-specific recognition protein (cis-DDP SSRP) binds selectively to double stranded DNA fragments modified by cis-DDP, {Pt(en)Cl 2 } ("en" refers to ethylenedia ine) or {Pt(dach)Cl 2 > ("dach" refers to 1,2-diaminocyclohexane) , but not to DNA modified with either trans-DDP or {Pt(dien)Cl}Cl ("dien" refers to diethylenetria ine) . It is important to note that the latter two platinum compounds are clinically ineffective and are unable to form 1,2-intrastrand dinucleotide adducts, whereas the first three compounds are capable of forming this type of DNA structural motif. The major DNA adducts of cis-DDP or cisplatin are d(GpG) and d(ApG) 1,2- intrastrand cross-links, which represent 65% and 25% of all such adducts, respectively. Thus, SSRP described herein binds specficially to these intrastrand d(GpG) and d(ApG) adducts. It is likely that SSRP (or a similar factor) also binds to DNA which has been damaged by other means, such as other genotoxic agents, which result in the formation of motifs comprising intrastrand cross-links and/or the introduction of platinum into the DNA. SSRP may recognize a strutural motif common to certain platinum-DNA adducts and to other types of DNA damage. It is also possible that it recognizes sequences which form tertiary DNA structural domains or motifs comprising sites of specific protein-DNA interactions. It is of interest to note that although prokaryotic DNA repair systems have been identified, comparatively little is known about corresponding factors that process damaged DNA in eukaryotic cells. Friedberg, E.C., DNA Repair. (W.H. Freeman and Co., New York (1985). From the information available, however, it appears that mamalian DNA repair enzymes possess damage-specific DNA binding properties, ibid.. pp. 150-152. In other words, repair enzymes and possibly other components of the cellular DNA repair machinery bind selectively to DNA structural motifs associated with DNA damage or lesions. The studies described herein were initially designed to investigate the hypothesis that in eukaryotic cells there is a structure-specific DNA binding factor or recognition protein with sufficient generality to recognize cisplatin- modified DNA as an initial step in the DNA-lesion repair process. These studies culminated in the discovery of a eukaryotic cellular factor (SSRP) in mammalian cells, both human and non-human, which selectively recognizes and binds a DNA structural motif associated with DNA damage. It follows that the factor described herein, alone or in conjunction with other cellular constituents, could be of general importance in the initial stages of processing of eukaryotic DNA which has been damaged by a genotoxic agent, such as cisplatin, and may belong to a wider class of cellular damage- or structure-specific recognition proteins. The cis-DDP SSRP has been shown to be present at least in human (i.e., HeLa) and non-human (i.e., hamster V79) mammalian cells and it should be emphasized that the cis-DDP binding factor occurs and produces approximately the same electrophoretic band shift in all cell lines tested. cis-DDP SSRP may be ubiquitous to all eukaryotic cells. Thus, the existence of at least one factor which specifically recognizes and binds to a damaged DNA structural motif has been demonstrated. It is important to note that the factor selectively recognizes a DNA structural motif produced by the interaction of an antitumor drug with DNA. Little or no binding of the cellular cis-DDP SSRP to unmodified (unplatinated) DNA occurs. Cellular cis-DDP SSRP binding to DNA fragments containing the above platinum adducts could be observed using damaged DNA fragments having as few as two platinated DNA lesions per 1,000 nucleotides. Low levels of binding to singled stranded DNA modified by cis-DDP were also observed. Although SSRP is described herein in the context of its ability to bind DNA damaged by an exogenous agent (a specific anticancer drug, cisplatin) it is likely that it, or a functional equivalent thereof, has a wider, more generalized role in DNA recognition and processing. This conclusion is based upon the fact that nature could not have evolved a system specific only for a particular drug or its adducts. That is, it is likely that the SSRP identified and described herein or a similar factor (i.e., one which has a similar specificity for and ability to bind to damaged DNA) interacts with DNA damaged by other means (e.g., spontaneous damage, environmental damage). Turning now to the method by which SSRP was identified, cellular extracts were assessed for the presence of the cis-DDP SSRP by a method comprising two independent, mutually corroborative techniques. One of these was a modified Western blot analysis (also known as Southwestern blotting) wherein electrophoretically resolved, blotted cellular proteins were renatured in situ (i.e., on the blot surface) and assessed for the ability to bind to a 32 P-labelled, damaged DNA fragment, (e.g., comprising at least one cisplatin-DNA adduct) . A protein identified as cellular cis-DDP SSRP by its ability to form a (damaged DNA fragment) : (protein) complex on the blot surface was observed to have an apparent molecular weight of approximately 100 000 daltons; these results are described more fully in the Examples which follow. The other technique relied upon in the present method of identifying SSRPs was electrophoretic gel mobility shift assay (EMSA, also known as bandshift analysis) . Initially, cell extracts were incubated in the presence of a 3 P-labelled, damaged DNA fragment (e.g., comprising at least one cisplatin-DNA adduct) and subjected to electrophoretic resolution, whereupon a (damaged DNA fragment) : (protein) complex formed in solution was detectably resolved from the soluble, damaged DNA fragment alone. This analysis for the presence of SSRP was further refined by EMSA studies wherein chemically synthesized oligonucleotide probes containing predefined chemical DNA adducts were used to characterize the εtructual features of platinated DNA which comprise the motif recognized by the cellular SSRP. These studies demonstrated that the 1,2-intrastrand d(GpG) and d(ApG) aducts formed by cis-DDP were specifically recognized by the cis-DDP SSRP. A competitive EMSA technique also allowed the determination of the dissociation constant (which is the reciprocal of the binding constant to platinum-damaged DNA) and other properties of the cisplatin SSRP. With this technique, it was demonstrated that the dissociation constant for in-solution formation of a (damaged DNA fragment) : (protein) complex is in the range of (1-20) x 10" 10 M, and that the protein described herein as cellular cis-DDP SSRP has an apparent molecular weight of about 91 000 daltons. It should be emphasized that the method of identifying SSRPs, while described herein with specific reference to the identification of at least one factor which selectively binds cisplatin-da aged DNA, can be used to identify and characterize other DNA structure-specific recognition proteins. For example, the present method can be used to identify other DNA SSRPs which hybridize to a particular probe, such as a cis-DDP- odified DNA restriction fragment, which has been previously shown to identify a factor which binds a particular type of damaged DNA (e.g., cisplatin-damaged DNA). If lower stringency conditions are used, for example, the probes described herein can be used to identify other DNA SSRPs (possibly also including factors which bind DNA damaged through the action of another chemical agent or radiation) . Both of the above techniques are described more fully below, particularly in the Examples. The similarity of the molecular weights of the cellular proteins identified by these two independent techniques supports the conclusion that, in each case, the same SSRP is observed. Further support is derived from the fact that the two have the same binding specificities for DNA modified with different platinum compounds. The cloning and characterization of human, Drosophila melanogaεter and Saccharomyces cereviεiae cDNAs encoding a protein having the characteristics of the cellular SSRP is also described below. I. Electrophoretic Mobility Shift Analysis A gel electrophoretic mobility shift assay (EMSA) was used in conjunction with radiolabelled DNA restriction fragments or chemically synthesized oligonucleotide probes containing specific, predefined platinum-DNA adducts, to characterize the structural features of platinated DNA which are specifically recognized by the structure specific DNA recognition protein (SSRP) described herein. EMSA, also known as bandshift analysis, was originally described as useful for characterizing mammalian transcriptional control factors. Fried, M. and D.M. Crothers, Nucleic Acids Res. 9:6505-6525 (1981); Singh, H. et al . , Nature, 319:154-158 (1986). Specific DNA-binding factors in a complex mixture of proteins have been identified by this technigue through the use of recognition sites containing 32 P-labeled DNA fragments in the presence of a large molar excess (e.g. 10 4 -fold) of competitor DNA, such as poly(dl-dC)"poly(dl-dC) . Briefly, the studies described in Examples A-K resulted in identification and characterization of a cellular protein that selectively recognizes a DNA structural motif produced by the interaction of particular platinum compounds with DNA. In particular, this work has elucidated several key properties of a cellular protein that binds selectively to DNA modified with the antitumor drug cis-DDP. The platinum damage- or structure-specific recognition protein may be part of a DNA repair complex or it may be a cellular constituent that responds to structural elements that occur or arise naturally in the genome. For present purposes, it is not important to distinguish between these two possibilities. However, it should be emphasized that since it is unlikely that biological systems would evolve a protein to complex with cisplatin adducts specifically, cis-DDP SSRP probably recognizes a naturally-occurring structural motif common both to certain platinum-DNA adducts and to other types of DNA damage, or possibly to sequences which form tertiary DNA structural domains that are the sites of specific protein-DNA interactions. The results of EMSA studies described in Example A demonstrate the existence of a cellular factor that binds with selectivity to cisplatin-DNA adducts. The slower migration through the gel of platinated DNA associated with (i.e., complexed with) the DNA-binding factor allowed it to be readily visualized. The factor was identified in nuclear extracts from human HeLa and Chinese hamster V79 parental and cis-DDP-resistant (adapted to 15 μg/mL cis- DDP) cell lines. Selectivity of binding was demonstrated by the positive correlation between the extent of binding and the extent of DNA modification. A minimum modification level of 0.007 Pt/nucleotide was required to observe binding of the factor to labeled platinated DNA, whereas at a modification level of 0.06 Pt/nucleotide, nearly all labeled DNA was complexed. For probes of higher r b (ratio of bound Pt per nucleotide) values, two bands are observed in the gel. This result may indicate the binding of two equivalent cellular factors to those DNA molecules having higher numbers of damaged sites. Cisplatin-damaged DNA fragments incubated with nuclear extracts from either V79 parental or resistant cell lines were bound to a similar extent, suggesting that its expression is not associated with an acquired resistance to cis-DDP. The results also revealed the presence of a factor causing approximately the same magnitude of band shift in cell extracts obtained from two dissimilar species, supporting the postulate that a similar (e.g., highly conserved) factor was being observed in both species. The cis-DDP specific DNA-binding factor has also been found in nuclear extracts from human B cells and from cytosolic extracts prepared from HeLa cells. A preliminary study of the selectivity of the cellular DNA binding factor for cis-DDP DNA adducts is described in Example B. The results of this study showed that the cellular factor bound selectively to DNA modified with cis-DDP, but not to DNA modified with either tranε- DDP or {Pt(dien)Cl}Cl. The nature of the structural motif selectively recognized by SSRP was further elucidated in a more refined EMSA selectivity study, discussed in Example G. These results demonstrated that the cellular SSRP binds selectively to DNA modified with cis-DDP, {Pt(en)Cl 2 }, and {Pt(dach)Cl 2 }, but not to DNA modified with either tranε- DDP or (Pt(dien(Cl) }C1. It is important to note that the latter two platinum compounds are unable to link adjacent nucleotides in DNA, whereas the former three are known to form 1,2-intrastrand d(ApG) and d(GpG) adducts. These results directly support the conclusion that SSRP selectively recognizes a DNA structural motif comprising a 1,2-intrastrand dinucleotide adduct. A preliminary competitive binding experiment, described in Example C, was performed to assess the specificity and affinity of the cellular factor for ciε- DDP-treated DNA. The results showed that binding of the cellular factor to a radiolabelled, cis-DDP-modified 274 bp restriction fragment of DNA prepared from the plasmid pSTR3 was effectively competed by increasing quantities of an unlabelled, cis-DDP-modified 422 bp restriction fragment derived from M13mpl8 DNA. Binding could be completely competed with a 100-fold excess of unlabeled modified DNA; however, unmodified 274 bp fragment did not compete for binding of the cellular factor. From the data obtained, the equilibrium constant for binding of the platinated DNA to the cellular factor was initially estimated to be 3 x 10* Kr l . Mtiller, R., Methods in Enzymology. 92:589-601 (1983). The same analysis provided an estimate of the concentration of the factor in crude extracts of approximately 4 x 10' 9 M. Ibid. Similar results were obtained when the labeled 274 bp fragment was competed with unlabeled 274 bp fragment modified to the same extent. The results of a subsequent competition study, discussed in Example F, demonstrated that the true value of the dissociation constant of the cellular factor identified as SSRP for its ligand, a particular DNA structural motif produced as a result of cis-DDP DNA adduct formation, lies in the range (1-20) x 10' 10 M. A displacement assay was also performed in which 0.1 ng of radiolabelled, cis-DDP-modified DNA (0.035 Pt/nucleotide) was incubated with 7.3 μg of nuclear extract from cis-DDP-resistant cell lines at 37°C for 15 minutes. Subsequently, varying concentrations of unlabelled, modified DNA were added to the mixtures and incubation was continued for an additional 15 minutes. In contrast to the results from the above competition assays, results of the displacement assay showed that the cellular factor remained bound to the labelled, platinated DNA even in the presence of a 1000-fold excess of unlabelled, platinated DNA. The competitive EMSA approach was also successfully employed for a concurrent analysis of the specificity and affinity of the cellular structure-specific recognition protein for cis-DDP-treated DNA. In this study, discussed in detail in Example H, synthetic DNA fragments containing predetermined types of platinum-DNA adducts were prepared from the oligonucleotides depicted in Figure 1. These fragments were radiolabelled and used in EMSA binding reactions in conjunction with an unlabelled competitor DNA fragment, comprising the 422 bp restriction fragment described in Example A, either untreated or treated with cis-DDP. The results of this competitive analysis revealed that SSRP binds selectively to DNA modified with the antitumor drug cis-DDP and that it is specific for the 1,2-intrastrand d(GpG) and d(ApG) adducts formed by cis- DDP. In contrast, SSRP does not recognize the 1,3- intrastrand d(GpTpG) adducts formed by ciε- and trans-DDP, nor does it recognize a monofunctional adduct formed by {Pt(NH 3 ) 2 (N3-cytosine} 2+ at the N7 position of deoxyguanosine. As noted previously, the ciε 1,3- intrastrand d(GpTpG) adduct unwinds the DNA helix to a much greater extent than the 1,2-intrastrand d(GpG) and d(ApG) adducts of this drug. This 1,3-intrastrand cross- linked adduct may therefore unwind the helix too much for SSRP recognition. Furthermore, the possibility that an amino acid residue of SSRP interacts directly with the platinum atom is unlikely since the protein does not bind to DNA modified with structurally distinct (e.g., interstrand or monofunctional) DNA adducts having a platinum atom as a common element. The above-described studies did not conclusively exclude the possibility that the cellular factor observed to bind selectively to platinated DNA might actually recognize a single-stranded domain adjacent the platinum- DNA adducts. Recognition of ss DNA was affirmatively excluded by a competitive EMSA study (Example I) in which nuclear extracts from HeLa cells were presented with unlabelled, ss M13mpl8 DNA in addition to the putative platinated DNA ligand, represented by the above radiolabelled, platinated 274 bp double-stranded restriction fragment. The ss M13mpl8 DNA did not compete for binding of the cellular factor, indicating the absence of a ss DNA binding factor. As noted previously, cyclobutane-type pyrimidine dimers formed by UV irradiation also have been suggested to bend the DNA helix by 30°, probably in the direction of the major groove. Recently, Chu and Chang reported the presence of a factor in nuclear extracts prepared from HeLa cells that binds specifically to DNA damage induced by UV irradiation. Chu, G. and E. Chang, Science 242:564- 567 (1988) . A study was initiated to test the logical hypothesis that SSRP and the factor described by Chu and Chang recognizes a common structural motif: a helical bend or kink of about 30° in the direction of the major " groove. The results of this EMSA study, which relied upon differential competition between cis-DDP modified and UV- damaged DNA fragments, are set forth in Example J. The results of this comparison, reported in Donahue, B.A. et al. (1990), Biochemistry 29:5872-5880, demonstrate that the DNA binding factor described herein as cis-DDP SSRP does not recognize DNA lesions induced by UV light. Therefore,- the structural motif recognized by cis-DDP SSRP does not correspond to the type of lesion produced by the irradiation of DNA with UV light. The conclusion can be drawn from the above EMSA studies that the cellular cis-DDP SSRP does not specifically recognize 30-34° kinks in the helix, nor does it simply respond to the presence of ss DNA formed opposite the cisplatin lesion, as evidenced by the failure of ss DNA to compete with platinum-modified DNA for binding. The protein may, however, recognize a particular combination of directed helix axis bending and local unwinding at the site of platination in 1,2-intrastrand cis-DDP-DNA cross-links. II. Modified Western Blotting Analysis In an alternative approach to the EMSA technique described above, modified Western (i.e., Southwestern) blotting was used to identify a factor, present in HeLa cells, which selectively binds to DNA modified by cis-DDP or {Pt(en)Cl 2 }. This technique is described more fully in Example L. Southwestern blotting analysis allowed a determination of the apparent size of the cellular protein having the ability to form (damaged DNA fragment) : (protein) complexes with platinum-modified DNA fragments. SSRP was observed to have an electrophoretic mobility corresponding to a molecular mass of approximately 100 000 daltons for a globular protein. Only double-stranded DNA restriction fragments modified by cis-DDP or {Pt(en)Cl 2 } bound selectively to the human cellular SSRP. A low level of SSRP binding to single stranded (ss) DNA modified by cis-DDP was observed, and little or no detectable binding was seen when unmodified single or double stranded DNA restriction fragments were used as probes for the blotted proteins. No appreciable binding to the factor, using DNA modified with the clinically ineffective trans-DDP or {Pt(dien)Cl}Cl compounds, was observed, compared with results for unplatinated control DNA. It should also be noted that a molecular species of about.M- = 28 000 daltons also bound a significant amount of the cis-DDP and {Pt(en)Cl 2 } modified DNA fragments with which the Southwestern blots were probed. Initially, it was thought that this factor arose through proteolytic degradation of the cellular SSRP. Results of subsequent investigations suggest that this factor is, or is related to, the known protein HMG-1. Southwestern blotting studies also demonstrated that extent of (damaged DNA fragment) : (protein) complex formation depended upon the level of DNA modification by cis-DDP. In addition, the Southwestern blotting system described herein was found to have a detection limit for SSRP of approximately 2 platinum adducts per 1000 nucleotides, also expressed as an r b level of 0.002. This technique was also used, as described below, for screening a human cDNA expression library for the presence of transcripts corresponding to pol peptides having SSRP activity. Further Characterisation of the Cellular SSRP The chemical nature of the cellular factor observed in HeLa cells was also assessed, by treating cytosolic extracts with either proteinase K or RNases, as described in Example D. Pretreatment of crude extracts with proteinase K resulted in loss of binding activity, confirming that the factor is a protein. Pretreatment of crude extracts with RNase A also resulted in a loss of activity, however, this sensitivity disappeared after partial purification of the cis-DDP-DNA binding factor by ammonium sulfate fractionation and ion exchange chromatography as described below. A study was carried out, as described in Example E, with the object of assessing the possible requirements of (damaged DNA fragment) : (protein) complex formation as observed in EMSA studies with the cellular SSRP for certain metal ions or cofactors. No specific cofactor dependencies were revealed, however SSRP binding was observed to be inhibited by the presence, during the EMSA incubation step, of metal ions that have an affinity for sulfur donor ligands. This suggests that thiol moieties present in the protein may be involved at or near the site(s) of SSRP-DNA structural motif interaction. The cellular protein identified as SSRP based upon its ability, observed in EMSA studies, to form (damaged DNA fragment) : (protein) complexes with a soluble DNA fragment containing at least one 1,2-intrastrand dinucleotide adduct, was partially purified and subjected to preliminary characterization by sucrose gradient sedimentation as discussed in Example K. Fractions obtained from the sucrose gradient were assessed in paralell by SDS-PAGE and EMSA. These results, summarized in Figure 2, indicated that the protein having SSRP activity has a sedimentation coefficient of 5.65, corresponding to an apparent molecular weight of 91 000 daltons for a globular protein. Thus, as described herein, DNA structure specific recognition factor, which has been shown to be a protein, has been identified in mammalian cells, using two independent, corroborative approaches. The DNA structure specific recognition protein has been shown to bind selectively to DNA modified with cisplatin and to bind specifically to intrastrand d(GpG) and d(ApG) DNA adducts formed by cis-DDP. The protein may be involved in initial recognition of damaged DNA as part of a repair event. Alternatively, it may be part of the cellular response to stress, may be involved in maintaining the tertiary structure of DNA, or may initiate or suppress a DNA- directed function at a specific structural motif. It should be emphasized that cis-DDP SSRP occurs and produces approximately the same band shift in all cell lines tested; hence, it may be ubiquitous to all eukaryotic cells. The apparent molecular mass of SSRP as observed in the two techniques employed for identification of the factor are 91 000 daltons and 100 000 daltons (by EMSA and Southwestern blotting analysis, respectively). Further anaylsis, using known techniques, is expected to demonstrate conclusively whether the 100 000 dalton and the 91 000 dalton proteins identified by the two methods are, in fact, the same protein or are two members of a family of functionally related SSRPs. In either case, SSRP can be used to produce substances, as described herein, useful in the treatment (prevention, reduction) of DNA damage by genotoxic agents, such as anticancer drugs. Cloning of SSRP from a cDNA Expression Library by a Modified Western Blot Screening Procedure The above-described selective binding of the HeLa cellular factor to DNA modified by cis-DDP suggested that it might be possible to isolate cDNA clones encoding the factor using cis-DDP-modified DNA as a probe. This approach proved fruitful: from a primary screen of 360,000 phage plaques, two recombinant phage, λPtl and λPt2, were isolated from a human B cell expression library based upon the results of a Southwestern blot screening assay. This Southwestern blot screening assay is described below in Example H; it was based upon the use of a radiolabelled 422 bp DNA restriction fragment modified by cis-DDP to an r„ level of 0.040 (discussed in Example A). E. coli lysogens (Y1089) containing the recombinant λPtl gene were deposited on September 22, 1988 at the American Type Tissue Culture Collection, 12301 Parklawn Drive, Rockville, MD 20852, USA, under the terms of the Budapest Treaty and assigned accession number 40498; upon granting of a U.S. Patent all restrictions upon access to this deposit will be removed. Restriction maps of the λPtl and λPt2 inserts are presented in Figure 3. The two clones have insert sizes of 1.44 and 1.88 kb (for λPt2 and λPtl, respectively) and are aligned at their 5' ends (see also Example 0) . A consequence of the method by which these clones were isolated (i.e., a functional assay which depended upon the presence of polypeptides capable of binding the selected ligand, a cisplatin-damaged DNA fragment), the shorter clone, λPt2, serves to more precisely delimit the polypeptide sequence responsible for cis-DDP SSRP binding activity. The polypeptides encoded by the recombinant phage have been assessed by Southwestern blotting analysis, described in Example N. A comparative study demonstrated that the recombinant polypeptides exhibit DNA binding properties similar to those of the cellular factor identified by Southwestern blotting studies of crude extracts prepared from mammalian cells. Expression of the Cellular βene Encoding λPt2 Northern blot analysis of cytoplasmic RNA was carried out using clone λPt2 as a hybridization probe (Example P) for the presence of RNAs encoding cellular SSRP. An initial study revealed the presence of a 2.8 kb mRNA which is conserved at least between humans and rodents. The . predicted molecular mass of the protein encoded by this mRNA transcript is 100 000 daltons, a size which correlates well with the results, discussed above, of modified Western blot analysis. See also, Toney, J.H., et al . (1989), Proc. Nat. Acad. Sci. USA 86:8328-8332. Further studies revealed an expression pattern for the SSRP gene which is consistent with a function that is critical to a variety of tissues. Its presence does not correlate with the tissue-specific antitumor activity of cisplatin, however, nor with drug sensitivity in a series of resistant cell lines. Moreover, expression of the encoded message was not inducible in HeLa cells treated with a range of drug concentrations. The Pull-Length cDKA Sequence of Human SSRP was obtained by Screening cDNA Libraries with Clone λPt2 As noted previously, λPt2, the shorter of the two clones obtained initially by using a functional screen (based upon protein binding to cisplatin-modified DNA) , served to define the region of SSRP responsible for DNA structual motif binding activity. As discussed below in Examples Q, R and S, the two clones obtained from Southwestern blot screening of a human cDNA expression library were in turn successfully employed as hybridization probes for the presence of additional SSRP sequences in several human cDNA libraries. The results of Southern blotting studies of the additional clones isolated in this manner are summarized in Figure 4. Sequencing studies, described in Example S, allowed the construction of a predicted amino acid sequence of the human DNA structure specific recognition protein, and revealed the presence of several distinct regions. The full length nucleic acid sequence, together with the predicted amino acid sequence encoded therein, are shown in Figure 5. Several functional domains observed in the encoded protein are schematically illustrated in Figure 6. The polypeptide encoded by λPt2 extends from residues 149- 627 of the full length protein, and includes the acidic domain, Basic I, and the HMG box. The latter domain comprises a region having interesting homologies to other proteins that recognize altered DNA structures, and thus is considered to be the domain of SSRP most likely to contain the site which selectively recognizes and binds to the 1,2-intrastrand dinucleotide structural motif produced by the interaction of cis-DDP with DNA. Proteins found to have sequence homology to SSRP include the high mobility group (HMG) proteins 1 and 2. Eink, L. and Bustin, M. (1985) Exp. Cell Res. 156:295-310; Bustin, M. , Lehn, D.A. and Landsman, D. (1990) Biochi . Biophγs. Acta 1049:231-243; van Holde, K.E., in Chromatin. Springer-Ve lag, NY (1988). Homology is also observed with the HMG-box domain in human upstream binding factor (hUBF) , which activates transcription of RNA poly erase I. Jantzen, H.M. , Admon, A., Bell, S. and Tijan, R. (1990) Nature 344:830-836. Other recently identified HMG-box proteins include sex- determining region Y (SRY) (Sinclair, A.H. , Berta, P., Palmer, M.S., Hawkins, J.R., Griffiths, B.L., Smith, M.J., Foster, J.W. , Frischauf, A.-M., Love11-Badge, R. and Goodfellow, P.N. (1990) Nature 346:240-244; Gubbay, J. , Collignon, J. , Koopman, P., Capel, B. , Econo ou, A., Munsterberg, A., Vivian, N. , Goddfellow, P. and Lovell- Badge, R. (1990) Nature 346:245-250) . mitochondrial transcription factor II (Parisi, M.A. and Clayton, D.A. (1991) Science 25:965-968), lymphoid enhancer binding factor I (Lef-1) (Travis, A., Amsterdam, A., Belanger, C. and Grosschedl, R. (1991) Genes & Dev. 5:880-894), a T- cell specific transcription factor (TCF-lα) (Waterman, M.L., Fischer, W.H. and Jones, K.A. (1991) Genes & Dev. 5:656-669), and the yeast autonomously replicating sequence factor ABF2 (Diffley, J.F.X. and Stillman, B. (1991) Proc. Nat. Acad. Sci. USA 88:7864-7868). A particularly interesting report is that of Shirakata, M. , Hϋppi, K. , Usuda, S., Okazaki, K. , Yoshida, K. and Sakano, H. (1991) Mol. Cell. Biol. 11:4528-4536, wherein the cloning of a mouse cDNA encoding an expression product capable of binding to V(D)J recombination signal sequence (RSS) probes is disclosed. The sequence of the protein encoded by this murine cDNA is 95.5% homologous to that of the human SSRP; presumptively, it is the murine homolog of SSRP as described herein. An additional factor which supports the idea that the HMG-box contains the cisplatin-DNA adduct structure specific recognition site is that HMG-1 binds strongly and specifically to cisplatin-modified oligonucleotides. Furthermore, Scovell, W.M. (1989) J. Macromol. Sci.-Chem. A26:455-480 and Hayes, J.J. and Scovell, W.M. (1991) Biochim. Biophys. Acta 1088:413-418 have concluded that cisplatin forms covalent cross-links between DNA and the proteins HMG-1 and -2. The biological relevance of this emerging family of HMG-box proteins, and of SSRP in particular, is discussed more fully below. Evolutionary Conservation of the Eukaryotic SSRP gene A Southern blot study was carried out with the object of determining the extent of evolutionary conservation of the DNA structure specific recognition protein described herein. For this purpose, a "zoo" blot comprising electrophoretically resolved DNA from a large number of species (generously donated by Dr. Paula Fracasso, in the laboratory of Professor David E. Housman, MIT) was probed with the 1.44 kb human cDNA clone, λPt2. Homologous sequences were observed in DNA derived from chimpanzee, monkey, elephant, pig, dog, rabbit, mouse, opossum, chicken, fish, and the fruitfly, Droεophila melanogaεter. Conversely, no hybridization was observed to DNA prepared from the nematode Caenorhabditiε eleganε, yeast, the parasite Giardia (which retains both prokaryotic and eukaryotic characteristics) , or the prokaryotic organisms Pεeudomonaε and Streptomyceε . Identification and Characterization of a Full-length Droεophila melanogaεter SSRP cDNA Sequence The studies presented herein demonstrated clearly that cis-DDP SSRP was evolutionarily conserved at least among mammalian species, such as humans and rodents (J.H. Toney, et al . , Proc. Natl. Acad. Sci. USA 86:8328 (1989); Shirakata, M. , Hϋppi, K. , Usuda, S., Okazaki, K. , Yoshida, K. and Sakano, H. (1991) Mol. Cell. Biol. 11:4528-4536), and that homologs exist in several other vertebrate species (see preceeding section) . The presence of an SSRP homolog in the invertebrate fruit fly, Droεophila melanogaεter, was of particular interest. Since regions of proteins that remain intact through evolutionary distance are generally critical for functional activity, the cloning of homologs from lower species often sheds light on the cellular role of the protein. For this reason, a low stringency screen of a Drosophila head cDNA library was conducted by using the original human cDNA clone λPt2 as a probe (described below in Example T) . From the pool of ten clones originally isolated, two cDNA clones were chosen for further study (see Example U) . Sequence analysis of these clones, denoted DM 3002 and DM 1001, revealed a significant region of overlap, shown in Figure 7. Within these cDNAs is contained all of the coding sequence of the Drosophila protein. These findings are discussed more fully below in Example V; the full length sequence of the Drosophila nucleic acid and the predicted amino acid sequence of the protein encoded therein are shown in Figure 8. The human DNA structure-specific recognition protein and its Drosophila counterpart share extensive homology at both the DNA and protein level. Both proteins contain a high percentage of charged amino acids that are concentrated within a few domains (illustrated in Figure 9) . Sequence analysis revealed that both proteins can potentially undergo a high degree of post-translational modification, with several phosphorylaton and one glycosylation site conserved between species. As noted previously in connection with the human protein, both the human and the Drosophila homologs of SSRP share homology with high mobility group proteins 1 and 2, with hUBF (a transcription factor containing an HMG-box domain) and with the transcriptional activator nucleolin. With great interest, it was observed that the structure of cis-DDP structure-specific recognition protein has also been conserved through evolution: Figure 9 shows that all charged domains and the HMG-box are located in the same relative positions in the human and the fly. These domains in the carboxy terminal half of the protein are clearly critical for the function of this structure- recognition factor, but it is important to note that extensive homology also exists in the less well understood amino terminal portion. As discussed more fully below, the dramatically high level of evolutionary conservation of this protein strongly supports the idea that it must provide a crucial intracellular function. Identification and Characterisation of a Saccharomyces cerevisiae protein having cis-DDP SSRP-Iike Activity; Isolation of a cDNA Sequence Encoding Same The yeast, S. cereviεiae, provides an excellent lower eukaryotic model system, especially for studies involving molecular genetic techniques to dissect the possible in vivo functions of SSRP. As discussed briefly above, a Southern blotting approach failed to reveal the presence of a yeast gene homologous to the human SSRP gene sequence encoded by clone λPt2. However, EMSA and Southwestern blotting investigations revealed the existence of at least one yeast cellular protein having cis-DDP SSRP-like activity. As discussed in Example Y, a Pt-DNA binding factor has now been purified from yeast whole cell extracts (YWCE) ; this has yielded samples enriched in SSRP specific activity, as assessed by EMSA or bandshift analysis. A Southwestern blot analysis of pooled bandshift active fractions from an S-Sepharose column corroborated that some active proteins appear to be enriched, relative to YWCE. In the first peak of bandshift activity, both a 42 000 and a 40 000 dalton protein are present. In the second peak of activity, these two proteins are also enriched, as well an 82 300 dalton protein and two smaller proteins of approximately 30 000 and 25 000 daltons. Bandshift activity that did not bind to a DEAE- sepharose column yields a similar modified Western blot banding pattern as the second peak of banshift-active proteins. It should be noted that, at present, it is difficult to correlate bandshift activity with Southwestern blotting results. However, it seems quite possible that several proteins are responsible for the observed bandshift activity. The small size of the known yeast proteins containing HMG-box domains, namely ABF2 (20 000 daltons) and NHP6 (11 400 daltons) has resulted in these proteins running off of the gels. (Kolodrubetz D. and A. Burgem (1990) -Journal of Biological Chemistry 265(6) :3234-3239; Diffley J.F.X. and S.B. (1991) Proceedings National Academy of Science. USA 88:7864- 7868). Thus, the proteins that are observed in Southwestern blots may be known proteins, or may be entirely novel. It is important to note that, in studies geared toward assessing the specificity of these proteins for platinated DNA structural motifs, it has been shown that the yeast proteins possess a binding specificity pattern similar to that found in HeLa extracts (see above) . Therefore, SSRPs present in yeast and humans may have similar biological relevance. Accordingly, a yeast genomic expression library was screened for the presence of expressed polypeptides capable of binding to a radiolabelled, platinated DNA fragment in the same manner as the above-discussed screening procedure which resulted in the isolation of the human cDNA clones λPtl and λPt2 from a human B cell expression library. This approach was successful: it resulted in the isolation of a single clone, λyPt, encoding a polypeptide having cis-DDP SSRP-like activity. A schematic illustration of clone λyPt is shown in Figure 10. The cloning and sequencing of this gene are described more fully below in Example AA; the yeast nucleic acid sequence and the predicted protein sequence encoded therein are shown in Figures 11 and 12, respectively. Northern blot analysis of total yeast RNA, using radiolabelled λyPt as a probe, demonstrated that the cloned DNA encodes a transcribed gene, resulting in a 2.1 kB mRNA. A translated protein of -78 kDa might possibly result from a mRNA of this size, thus the ySSRP is presumed at present to be the 82 000 dalton protein observed in Southwestern blots. It is important to note that since the open-reading frame contained within the λyPt sequence (discussed below) is 1.63 kB, approximately 0.5 kB of sequence is missing from the 5' end of the gene. A homology search with the partial or fractional ySSRP sequence encoded by clone λyPt resulted in the identification of regions of homology with numerous glutamine rich proteins. Interestingly, the polyglutamine region of transcription factor Spl is required for protein-protein interactions. Courey, A.J., D.A. Holtzman et al. (1989) Cell 59:827-836. A search limited to the non-glutamine rich portion of ySSRP, residues 282-510, yields a much more limited set of proteins. Almost all of these proteins belong to the recently discovered and rapidly growing class of proteins which contain the HMG- box domain. The highest degree of similarity is found to the yeast protein ABF2. ABF2 is contains two HMG-boxes and is highly related (37% identical, 65% similar) to ySSRP over 151 of its 183 amino acids. ABF2 binds to ARS1 domains that do not demonstrate consensus DNA sequences. Based on this fact, it has been suggested that ABF2 recognizes DNA structural features. Diffley, J.F.X. (1991) Proc. Nat. Acad. Sci. USA 88:7864-7868). Thus, like ABF2,- ySSRP may also be recognizing DNA structures. Sequence homology of ySSRP to the predicted amino acid sequence of the human SSRP is rather low, with only 12.7% identity and 38% similarity found with an optimal alignment. Moreover, alignment with the D. melangaster SSRP reveals the same level of homology (14.5% identical, 38% similar) to the yeast protein. Yeast ySSRP, like human SSRP, does contain HMG-box domains towards its carboxy terminus. Thus, this region is probably important for DNA structural motif recognition. The high glutamine content of the remainder of the ySSRP sequence suggests that it may be important in protein-protein interactions. or in protein oligomerization. This hypothesis may be enlarged to the human SSRP. Functional Significance of SSRP At present, the precise nature of the in vivo role of cis-DDP SSRP is unknown; however, mounting circumstantial evidence has been presented that it may play a significant part in the initiation or control of cellular processes responsive to specific DNA structural motifs. Thus, one possible role is to recognize sites of DNA damage as a signaling event for DNA repair. A current model for recognition of DNA damage by the E. coli ABC excision system is that UvrA forms a complex with UvrB, either in solution or after it has bound to DNA at a site of damage. Orren, D.K. & Sancar, A. (1989) Proc. Natl. Acad. Sci. U.S.A. 86: 5237-5241. UvrA then dissociates from DNA, and UvrB, in conjunction with UvrC, excises an oligonucleotide encompassing the damage. The resulting gap is then filled in with the correct nucleotides by DNA polymerase. It is reasonable to surmise, then, that if this model of the E. coli excision repair system is valid and if it can be extrapolated to eukaryotic DNA excision repair, SSRP may function in a manner analogous to UvrA. Regardless of whether this proposed in vivo role for SSRP is ultimately substantiated, the fact remains that cis-DDP SSRP has been demonstrated to posess the highly interesting and significant ability to bind selectively to a DNA structural motif produced by the DNA adducts of chemotherapeutically active platinum drugs, but not the adducts of two clinically ineffective platinum compounds. Moreover, the specific adducts recognized by SSRP (1,2- intrastrand dinucleotide adducts) comprise 90% of all cisplatin-DNA structures formed in vivo . These facts strongly support the conclusion that SSRP plays an important role in cellular recognition of, and response to, the presence of certain DNA structural motifs including those associated with DNA damage or lesions. It thus is reasonable to propose that if SSRP is a component of a repair complex, it will facilitate the antitumor effectiveness of cisplatin. For example, if tumor cells were deficient, relative to nontumor cells, in their ability to repair platinum-damaged DNA, the platinum drug would be selectively lethal to tumor cells, whereas repair-proficient surrounding cells would remove platinum adducts from their DNA and hence survive. This model, however, does not account for the anticancer utility of certain platinum drugs, such as {Pt(NH 3 ) 2 (N3-cytosine) } +2 , although it has been proposed that the latter compound could act through a different mechanism than cis-DDP. Alternatively, SSRP may not be involved in DNA repair at all. It may actually impede DNA repair by binding to the 1,2-intrastrand d(GpG) and d(ApG) adducts of cis-DDP, thereby shielding these adducts from the DNA repair machinery. Donahue, B.A., Augot, M. , Bellon, S.F., Treiber, D.K., Toney, J.H., Lippard, S.J. and Essigmann, J.M. (1990) Biochemistry 29:5872-5880. This proposed in vivo role for SSRP is consistent with its observed pattern of gene expression in different tissues, and in several cancer cell lines, including cisplatin-resistant cell lines. Still another possibility is that the normal role of SSRP is to regulate the function of genes implicated in the emergence of malignancies, or conversely in the maintenance of normal phenotypes. Platinum adducts, by providing DNA structural motifs which mimic those of the natural regulatory sequences of such genes, would displace SSRP from its normal DNA binding sites, thereby effectively sequestering the protein. Donahue, B.A. , Augot, M., Bellon, S.F., Treiber, D.K., Toney, J.H., Lippard, S.J. and Essigmann, J.M. (1990) Biochemistry 29:5872-5880; Scovell, W.M. (1989) J. Hacromol. Sci.-Chem. A26:455-480. It follows that, if tumor cells had lost the ability to compensate for this effect, cis-DDP would selectively compromise the welfare of tumor cells. As discussed previously, SSRP as described herein is a protein that recognizes a DNA structural motif comprising the 1,2-intrastrand dinucleotide adducts which are the predominant drug-DNA adducts formed as a result of the interaction of cis-DDP with DNA. These intrastrand d(GpG) and d(ApG) cross-links unwind the DNA duplex by 13° and cause a 34° bend in the direction of the major groove. Churchill, M.E.A. and Travers, A.A. (1991) TIBS 16:92-97; Bellon, S.F. and Lippard, S.J. (1990) Biophvs. Chem. 35:179-188; Rice, J.A. , Crothers, D.M. , Pinto, A.L. and Lippard, S.J. (1988) Proc. Nat. Acad. Sci. USA 85:4158- 4161. Important clues for identifying the type of protein that might interact with such an altered structure are provided by the striking homology of the human SSRP to HMG-1, which is known to bind cruciform DNA (Bianchi, M.E., Beltrame, M. and Paonessa, G. (1989) Science 243:1056-1058), and the near identity, at the protein sequence level, of the human SSRP disclosed herein and a mouse protein which has been reported to bind to signal sequences for V(D)J recombination. Shirakata, M. , Huppi, K. , Usuda, S., Okazaki, K. , Yoshida, K. and Sakano, H. (1991) Mol. Cell. Biol. 11:4528-4536. The common DNA structural element recognized by SSRP and HMG-1, while not yet defined, most likely mimics the unwinding and bending known to occur in cisplatin-modified DNA. Taken together, the observed properties of SSRP raise the possibility that HMG-1, the family of HMG-box proteins, and recombination functions may be involved in the molecular mechanism of the effective antitumor drug, cisplatin. Homology between SSRP as described herein and HMG-1 and -2 is particularly interesting because the latter proteins can also specifically recognize structural distortions to DNA such as B-Z junctions and cruciforms (H. Hamada and M. Bustin, Biochemistry. 24:1428 (1985); Bianchi, H.E. , et al. Science 243:1056 (1989)). They too are evolutionarily conserved, with homologs known in human (L. Wen, et al., Nucl. Acids Res.. 17:1197 (1989)), bovine (B. Pentecost and G.H. Dixon, Biosci ' . Rep.. 4:49 (1984); D.J. Kaplan and C.H. Duncan, Nucl. Acids Res.. 16:10375 (1988), porcine (K. Tsuda, et al . , Biochemistry. 27:6159 (1988)), rodent (G. Paonessa, et al . , Nucl. Acids Res.. 15:9077 (1987); K.-L.D., Lee, et al ., Nucl. Acids Res.. 15:5051 (1987)), fish (B.T. Pentecost, et al . , Nucl. Acids Res.. 13:4871 (1985)), yeast (D. Kolodrubetz and A. Burgum, J. Biol. Chem.. 265:3234 (1990), maize (K.D. Grasser and G. Feix, Nucl. Acids Res.. 19:2573 (1991)), and protazoa (S.Y. Roth, et al . , Nucl. Acids Res.. 15:8112 (1987); T. Hayashi, et al . , J. Biochem.. 105:577 (1989)). Many studies support a role for HMG-1 and -2 in DNA processing, particularly in transcriptional regulation. They influence transcription of RNA polymerase II and III by altering the DNase I footprint of the major late transcription factor, presumably by conferring a structure to the binding site which optimized the process (D.J. Tremethick and P.L. Molloy, J. Bio. Chem. f 261:6986 (1986); F. Watt and P.L. Molloy, Nucl. Acids Res.. 16:1471 (1988)). HMG-1 has also been shown to modify DNA structures, such as B-Z junctions and cruciforms, in in vitro transcription assays, thereby permitting transcription to proceed past these structural blocks (S. Waga, et al . , iochem. and Biophys. Res. Com .. 153:334 (1988); S. Waga, et al . , J. Biol. Chem.. 265:19424 (1990)). Other work has suggested that HMG-l and -2 can act as general class II transcription factors, and may be tightly associated with or identical to transcription factor IIB (J. Singh and G.H. Dixon, Biochemistry , 29:6295 (1990)). These studies, taken together, suggest that HMG-1 and -2 act to facilitate transcription by binding to specific DNA conformations to create or preserve structures necessary for transciption initiation. A salient feature of the cDNA clones identified as encoding SSRP is that each includes the region of nucleotide sequence identified as an HMG box domain. HMG box domains are emerging as an important recognition element of proteins for DNA. Deletion analysis of HMG-box family members hUBF (Jantzen, H.M., Admon, A., Bell, S. and Tijan, R. (1990) Nature 344:830-836) and TCF-lα (Waterman, M.L., Fischer, W.H. and Jones, K.A. (1991) Genes & Dev. 5:656-669) has demonstrated that a single HMG-box domain is sufficient for the specific interactions of these proteins with DNA. It is important to note, however, that in spite of the .. emergence of several proteins identified as HMG-box family members, a consensus sequence has not yet emerged for the HMG box domain. Lack of a clearly defined consensus sequence among the HMG-box domains in a variety of proteins may indicate either that such proteins recognize different DNA structures, or that they do not share a common mode of DNA recognition. Whereas mutations in the sequences of target recognition sites in DNA alter binding of the HMG-box proteins, such changes could also modify the shape of the recognition site, reducing its protein affinity. The suggestion (Diffley, J.F.X. and Stillman, B. (1991) Proc. Nat. Acad. Sci. USA 88:7864-7868) that HMG-box proteins recognize DNA structure rather than sequence is strongly supported by the observations reported herein, that SSRP binds selectively to cisplatin- modified DNA fragments, but not to unmodified fragments having the same sequence. Other properties of HMG-1 are fully consistent with its role in binding to altered DNA structures. For example, HMG-1 suppresses nucleosome core particle formation (Waga, S., Mizuno, S. and Yoshida, M. (1989) Biochim. Biophvs. Acta 1007:209-214), and it can selectively unwind negatively supercoiled DNA, thereby protecting it from relaxation by E. coli topoisomeraεe I and preventing the formation of higher order secondary structure (Sheflin, L.G. and Spaulding, S.W. (1989) Biochem. 28:5658-5664). It binds preferentially to A-T rich regions (Reeves, R. and Niεsen, M.S. (1990) J. Biol. Sciences 265:8573-8582), single stranded DNA (Iεackson, P.J., Fishback, J.L., Bidney, D.L. and Reeck, G.R. (1979) J. Biol. Chem. 254:5569-5572), B-Z junctions (Hamada, H. and Bustin, M. (1985) Biochem. 24:1428-1433), and to cruciform structureε (Bianchi, M.E. , Beltrame, M. and Paonessa, G. (1989) Science 243:1056-1058). Moreover, studies of plasmid DNA containing a number of εtructural domains suggest that HMG-1 can differentiate among various DNA conformations (Hamada, H. and Bustin, M. (1985) Biochem. 24:1428-1433). Of particular interest are several εtudieε which suggest that HMG-1 and -2 act by binding to specific structural elements in DNA upstream from actively transcribed genes to preserve conformations necessary for the binding of sequence-specific transcription factors. Tremethick, D.J. and Molloy, P.L. (1986) J. Biol. Chem. 261:6986-6992; Tremethick, D.J. and Molloy, P.L. (1988) Nucl. Acids Res. 16:1471-1486; Watt, F. and Molloy, P.L. (1988) N^cl ' Acids Res. 16:1471-1486; Waga, S., Mizuno, S. and Yoshida, M. (1988) Biochem. Biophys. Res. Comm. 153:334-339; Singh, J. and Dixon, G.H. (1990) Biochem. 29:6295-6302. In particular, HMG-1 removes the transcriptional block caused by cruciforms in supercoiled DNA. Waga, S., Mizuno. S. and Yoshida, M. (1990) J. Biol. Chem. 265:19424-19428. Eukaryotic DNA contains palindromic sequences that form cruciform structures, which may in turn have elements in common with the 1,2- intrastrand d(ApG) and d(GpG) adducts formed by cisplatin modified DNA. Additional insights into the posεible in vivo role of cis-DDP SSRP are provided by the recent characterization of a mouse cDNA clone isolated by screening an expression library with oligonucleotides containing recombination signal sequences (RSS) . Shirakata, M. , Hiippi, K., Usuda, S., Okazaki, K., Yoshida, K. and Sakano, H. (1991) Mol. Cell. Biol. 11:4528-4536. RSS εequenceε are signals for somatic DNA recombination to generate antibody diversity through V(D)J joining. The predicted amino acid sequence of this mouse protein is 95.5% identical with that of the human SSRP described herein. Therefore, it is presumed to be encoded by the mouse homolog of the human and Droεophila SSRP genes as disclosed herein. Interestingly, V(D)J recombination is postulated to proceed via stem-loop εtructureε formed by RSS εequences (Max, E.E., Seidman, J.G. and Leder, P. (1979) Proc. Nat. Acad. Sci. USA 76:3450-3454; Sakano, H., Hϋppi, K. , Heinrich, G. , and Tonegawa, S. (1979) Nature 280:88-94; Early, P., Huang, H. , Davis, M. , Calame, K. and Hood, L. (1980) Cell 19:981- 992; Tonegawa, S. (1983) Nature 302:575-581), although this model has been challenged (Hesse, J.E., Lieber, M.R. , Mizuuchi, K. and Gellert, M. (1989) Genes & Dev. 3:1053- 1061) . The similarity among stem-loop DNA, cruciforms recognized by HMG-1, and the bent, unwound cisplatin-DNA 1,2-intrastrand cross-link structural motif is intriging and supports the postulate that binding of the mouse HMG- box protein reported by Shirakata et al. to RSS involves shape as well as sequence recognition. When the present invention is viewed in the context of the foregoing remarks, it will be apparent that SSRP, and possibly other HMG-box proteins, may be diverted or sequestered from their normal regulatory intracellular roles by the presence of cisplatin-DNA adducts, and that somatic DNA recombination and transcription are specific cellular functions likely to be affected by the platinum anticancer drug family. Understanding the shape recognition elements of these proteins may provide a basis for the design of future generations of rationally designed chemotherapeutic agents. use of SSRP for diagnostic, therapeutic and prophylactic purposes As a result of the discovery embodied in this invention, new diagnostic tools are available, including, for example, nucleotide probes and antibodies which are useful for detecting the presence or absence of SSRP and/or of the gene or portion thereof which encodes SSRP. Antibodies prepared against the SSRP, or DNA or RNA probes which bind to DNA encoding the SSRP, may be useful for classifying the responεiveneεs of humanε or animals to DNA damaging agents. Antibodies against the DNA structure- specific regognition factor described herein have been generated by injecting a fusion protein (/S-galactosidaεe- λPt2) into rabbitε, in whom εpecific polyclonal antibodies were subsequently produced. These antibodies have been shown by Western blot analysis to bind the λPt2 fusion protein. These diagnostic tools can be used, for example, in prenatal screening. Thus, prenatal genetic screening for known genetic defects or genetic characteristics associated with particular diseases can now include assessment of the absence of SSRP, or of its occurence at altered (e.g., lowered) levels. Absence or abnormal (e.g., subnormal) expression of the SSRP is putatively indicative of the likelihood that the individual tested will develop cancer during life. The invention described herein also makes possible the production of a therapeutic agent useful in protecting an individual against DNA damage, or in countering DNA damage that has already occurred. For example, a therapeutic agent protective against the DNA structural or chemical damage caused by chemotherapy or radiotherapy can be administered to an individual prior to therapy, at the time of therapy (e.g., in the course of treatment of humans with radiation or with the anticancer drug cisplatin), or after such treatment has been undergone. The agent will protect against damage to DNA by creating a DNA damage-refractory phenotype. A further result of the present invention is that gene therapy or gene replacement will be available to individuals lacking SSRP or having less than normal expression levels of the factor. In such a case, DNA encoding SSRP can be administered to individuals by means of, for example, genetically-engineered vectors that contain the factor-encoding DNA and regulatory and expression components necesεary for its expression. Such recombinant vectors can be used, for example, to infect undifferentiated cells in situ in the individual. The resultant cells express the encoded factor (SSRP) , thereby overcoming the shortage or lack of natural DNA structure- specific recognition protein production in the individual. The present invention will now be illustrated by the following examples, which are not to be considered limiting in any way. Example A: Electrophoretic Mobility Shift Analysis (EMSA) of the DNA binding Characteristics of the Cellular cis-DDP Structure-Specific Recognition Protein (cis-DDP SSRP) Materials. Restriction endonucleases and polynucleotide kinase were purchased from New England Biolabs. The Klenow fragment of E. coli polymerase I and bacteriophage T4 DNA ligase (Boehringer Mannheim Biochemicals) , proteinase K and RNase A (Sigma) , (hexamethyldecyl)trimethylam onium bromide (CTAB) (Fluka), and poly(dl-dC) •poly(dl-dC) (Pharmacia) were obtained from commercial sources as indicated. The cell lines used were HeLa (kindly provided by. M. Chow, MIT), cis-DDP-resistant HeLa, Chinese hamster V79, and cis-DDP-resistant V79 cells (kindly provided by S.L. Bruhn, MIT; cis-DDP resistant V79 cells were adapted to 15 μg/mL cisplatin, making them about 30-fold more resistant than parental cells) , and human B cells (RPMI 4265; kindly provided by H. Singh, MIT) . Cell Extracts. Cytosolic, nuclear and whole-cell extracts were prepared according to published procedures. Stillman, B.W. and Y. Gluzman, Mol. Cell. Biol. 5:2051-2060 (1985); Dignam et al .. Nucleic Acids Res. 13:1475-1489 (1983); and Wood et al . , Cell 53:97- 106 (1983) , respectively. Protein concentrations were determined by the method of Bradford. Bradford, Anal. Biochem. 72:248-254 (1976). Platinum-Modified damaged DNA fragments. cis-DDP, trans-DDP, [Pt(en)Cl 2 ], and [Pt(dien)Cl]Cl were prepared as described (Johnson, G.L. Inorg. Synth. 8:242-244 (1966); Dhara, S.C., Indian J. Chem. 8:193- 194 (1970); Watt, G.W. and W.A. Cude, Inorq. Che . 7: 335-338 (1968); Lippard et al . , Biochemistry 22:5165- 5168 (1983) . Restriction fragments, a 274 bp Clal-Smal fragment generated from pSTR3 (see Couto et al . , S___. Bacteriol. 171:4170-4177 (1989)) and a 422 bp Aval fragment generated from bacteriophage M13mpl8 DNA, were purified on low melting point agarose electrophoresis gels followed by phenol extraction (Maniatis et al . , Molecular Cloning. A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1982)) or butanol extraction in the presence of CTAB (Langridge et al . , Anal. Biochem. 103:264-271 (1980)). Restriction fragments were suspended in 1 mM sodium phosphate buffer, pH 7.4, containing 3 mM NaCl (buffer B) or in TE at a DNA nucleotide concentration of about 10"* M. A portion of the DNA was allowed to react with the appropriate platinum complex at a variety of formal drug/nucleotide ratios at 37°C for 12-24 hours. An identical volume of buffer B or TE was added to control, unmodified DNA and incubated in parallel with the modified DNA fragment. Unbound platinum was removed by ethanol precipitation of the Pt-modified DNA restriction fragments, followed by several washes of the pellet with 80% ethanol. DNA concentrations were determined by UV spectroscopy with the relation 1 OD-jβo = 50 μg/raL. Bound levels of Pt to DNA were measured on a Varian AA-1475 atomic absorption spectrometer equipped with a GTA-95 graphite furnace. DNA fragments were radiolabelled with [o- 32 P]dCTP (>5000 Ci/mmol, New England Nuclear) by the Klenow fragment of DNA polymerase I. Labeled, damaged DNA fragments were purified on native polyacrylamide gels as described in Maniatis et al . , Molecular Cloning. A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. 1982) and resuspended in TE to 5000 cpm/μL prior to use in EMSA or other studies. Electrophoretic Gel Mobility Shift Assay (EMSA or bandshift analysis) . Studies of (damaged DNA frgament) : (protein) complexes formed as a result of binding of SSRP to radiolabelled, platinated DNA fragments with the use of gel electrophoresis was carried out as described by Carthew et al ., Cell 43:439-448 (1985) with minor modifications. End- radiolabeled DNA restriction fragments [(1-5) x 10 3 cpm; -0.2 ng] that were either unmodified or modified with the various platinum compounds as indicated below were incubated in the presence of crude extracts, typically 5-10 μg of protein, and 6 μg of competitor poly(dI-dC)*poly(dI-dC) for 15 minutes at 37°C in binding buffer (10 mM Tris-HCl, pH 7.5, 50 mM NaCl, 0.5 mM Na 2 EDTA, 5% glycerol, and 1 mM DTT) in a final volume of 10-50 μL. (Damaged DNA fragment) : (protein) complexes were thereafter resolved from uncomplexed DNA fragments on a 4% polyacrylamide gel [29:1 acrylamide:N,N , -methylene- bis(acrylamide) ]. Gels were preelectrophoresed in Tris-glycine buffer (50 mM Tris-HCl, pH 8.5, 380 mM glycine, 2 mM Na 2 EDTA) for >1 hour at 25 mA. Samples were then electrophoresed for about 4 hours at 30 mA. Gels were dried and autoradiographed overnight at -20°C wit an intensifying screen. The results of this study showed the binding of a cellular protein to a damaged DNA fragment comprising a radiolabelled, cis-DDP modified 422 bp Aval restriction fragment of M13mpl8 DNA. Radiolabelled DNA fragments (1-5 x 10 3 cpm; 0.2 ng) contained bound cis-DDP levels as follows: lanes 1-4, r b of 0; lanes 5-8, r b of 0.007; lanes 9-12, r b of 0.021; lanes 13-16, r b of 0.041; and lanes 17-20, r b of 0.061. These radiolabelled. platinum damaged DNA fragments were incubated in the absence (-; lanes 1, 5, 9, 13 and 17) or presence of crude nuclear extract prepared from V79 parental cells (VP; lanes 2, 6, 10, 14 and 18), cis-DDP-resistant V79 cells (VR; lanes 3, 7, 11, 15 and 19) or HeLa cells (H; lanes 4, 8, 12, 16 and 20). It was seen from the resulting autoradiograph that migration of the DNA fragment alone was retarded with increasing levels of modification (lanes 1, 5, 9, 13 and 17), owing to increased positive charge and increased structural alterations of the DNA as a result of cis-DDP binding. Sherman, S.E., and S.J. Lippard, Chem. Rev.. 87:1153- 1181 (1987) . It was also seen that that cellular factors present in HeLa nuclear extract bind to unplatinated DNA (lane 4) . This binding was reproducible, independent of the oligonucleotide probe, and currently of unknown origin. A second band also appeared with the unplatinated DNA probe (lane 1) and probably represents denatured probe DNA. In pertinent part, the EMSA results showed the presence of a cellular structure-specific DNA recognition protein (SSRP) which binds selectivity to cisplatin-modified DNA. This DNA binding protein formed a (damaged DNA fragment) : (protein) complex having a retarded electrophoretic migration relative to that of the damaged DNA fragment alone (e.g., lanes 1, 5, 9, 13 and 17), allowing the complex to be visualized in nuclear extracts from human HeLa and Chinese hamster V79 parental and cis-DDP-resistant cell lines. Selectivity for platinated DNA was demonstrated by the correlation between the extent of binding and the level of DNA platination. An estimated minimum modification level of about 0.007 Pt/nucleotide was required to observe binding of the protein to labeled modified DNA, whereas, at a modification level of 0.06 Pt/nucleotide, nearly all labeled DNA was complexed. For probes of higher r b , two bands were observed in the gel (lanes 18-20) , possibly indicating the binding of two protein molecules to those DNA fragments having higher numbers of damaged sites. In other experiments, cis-DDP- specific SSRPs were found in cytosolic extracts and whole-cell extracts prepared from HeLa cells and in nuclear extracts from human B cells. Cytosolic and whole-cell extracts from this latter source were not examined. It has not yet been conclusively established that the protein observed in cytosolic extracts is the same as that found in nuclear extracts. However, as described below, both proteins have similar specificities of binding to DNAs modified with various platinum compounds. Furthermore, both proteins are precipitated with 40-65% ammonium εulfate. It should also be noted that the cis-DDP SSRP appears to be present at the same levels in platinum- sensitive and platinum-resistant cell lines. Platinated DNA fragments incubated with nuclear extracts from either V79 parental or cis-DDP-resistant cell lines were bound to similar extent. Similar results were obtained with parental and approximately 50-fold cis-DDP-resistant HeLa cell extracts (data not shown) . Hence, in these cell lines the level of SSRP present does not seem to be related to acquired cellular resistance to cis-DDP. Example B: EMSA Study of the Selectivity Characteristics of the Cellular SSRP for cis-DDP An EMSA study was carried out with the object of assessing the ability of the SSRP disclosed in Example A to discriminate among different platinated DNA adducts. Here, the 422 bp Aval DNA restriction fragment described in Example A was modified with various platinum compounds and incubated in the absence (lanes 1, 5, 9, 13 and 17) or presence of crude extracts prepared from V79 parental cells (VP; lanes 2, 6, 10, 14 and 18), V79 cis-DDP-resistant cells (VR; lanes 3, 7, 11, 15 and 19) or HeLa cells (H; lanes 4, 8, 12, 16 and 20), all as described above in Example A. SSRP was observed to form complexes only with DNA fragments containing adducts of platinum drugs which are capable of forming 1,2-intrastrand dinucleotide adducts. Example C: Competitive EMSA Study of the Cellular SSRP A competition study was carried out wherein protein-DNA fragment binding reactions were incubated in the presence of escalating concentrations of unlabelled DNA fragments containing or lacking sites of platinum modification. More specifically, a preparation of end-labeled 274 bp Clal-Smal restriction fragment generated from pSTR3 as described above in Example A (5000 cpm; 0.2 ng) was modified with cis-DDP at r b = 0.045. Labelled DNA fragments were incubated in the presence of 7.3 μg nuclear extract from cis-DDP- resistant V79 cells, nonspecific competitor DNA, and competitors as follows: lanes 3-6 = 0.2, 1, 10 and 20 ng unlabeled, unmodified 422 bp Aval restriction fragment of Ml3mpl8; lanes 7-10 = 0.2, l, 10 and 20 ng unlabeled 422 bp fragment modified with cis-DDP at an r b level of 0.035. It was shown that the cis-DDP modified fragments were effective competitors, and that the corresponding unmodified fragments were ineffective. Example D: EMSA Study of the Sensitivity the Cellular SSRP to Protease and Ribonucleases A sensitivity study was designed to investigate the effects of incubation in the presence of protease or ribonuclease on the ability of the cellular SSRP to form (damaged DNA fragment) : (protein) complexes. The results obtained by EMSA analysis demonstrated that the cellular factor in crude extracts was sensitive to the activity of protease and ribonucleaεes. Crude nuclear extracts were pretreated at 37°C for 60 minutes in the presence or absence of enzymes. The pretreated extracts were then incubated with 5000 cpm (0.2 ng) end-labeled 422 bp Aval reεtriction fragment, modified with cis-DDP at an r b level of 0.041 aε deεcribed in Example A. Electrophoretically resolved samples included: lane 1, free unlabeled 422 bp platinated fragment; and lane 2, extract pretreated in the abεence of lytic enzymeε. The remaining lanes were as follows: lane 3 (P) , proteinase K at 100 μg/mL; lane 4 (M) , micrococcal nuclease at 0.075 U/mL; lane 5 (Tl) , RNaεe Tl at 0.025 U/mL; lane 6 (T2) , RNaεe T2 at 0.005 U/mL; laneε 7-10 (R) , RNaεe A at 20 μg/mL, 2 μg/mL, 0.2 μg/mL, and 0.02 μg/mL. In εubεequent studies, cell extracts and partially purified SSRP (described below) were incubated in the presence * of proteinase K at 100 μg/mL or RNase A at 20 μg/mL for 1 hour at 37°C in 10 mM Tris-HCl, pH 7.4, containing 1 mM Na 2 EDTA, then subjected to EMSA analysiε aε deεcribed in Example A. The reεultε of thiε εtudy εhowed that pretreatment of crude extractε with proteinaεe K resulted in loss of binding activity, confirming that the observed factor (SSRP) is a protein. Pretreatment of crude extracts with RNase A also resulted in loss of activity, but this εenεitivity disappeared after partial purification of the cis-DDP SSRP factor by ammonium sulfate fractionation and ion exchange chromatography as hereinafter described. Example E: EMSA Investigation of Possible Requirements of the Cellular cis-DDP SSRP for cofactors and metal ions The gel mobility shift assay was also used to assess the posεible cofactor and metal ion requirements for binding of SSRP to cis-DDP-modified DNA. The factor in crude cellular extracts required neither ATP nor divalent cations such as Mg + and was insensitive to EDTA at concentrations up to 100 mM. Binding activity was senεitive, however, to εome metal ions. (Damaged DNA fragment) : (protein) complex formation was completely inhibited in the presence of 5 mM ZnCl 2 , MnCl 2 , CoCl 2 , or CdCl 2 and by 1 mM HgCl 2 . The protein bound to platinated DNA at both 37 and 0°C, but heat treatment of the extracts (42°C for 15 minutes) prior to the EMSA incubation εtep (see Example A) resulted in complete loss of activity. SSRP binding activity was also inhibited at high salt concenrations, εuch as 500 mM KC1. Example F: Competitive Electrophoretic Mobility Shift Analysis of the Cellular SSRP Competition Assays. Competition assays were performed by adding various amounts of unlabeled competitor DNA to the binding reactions of the gel mobility shift asεay before the 15-min incubation step described in Example A. Competitor DNA was either a restriction fragment as described above, or M13mpl8RF (replicative form) DNA that was either unmodified or modified with cis-DDP or UV light. Determination of the Binding Constant of cis-DDP SSRP. The binding constant of the protein for platinated DNA was estimated as described by Mϋller, R. , Methods Enzvmol. 9:589-601 (1983). A competition assay was performed in which radiolabeled 274-bp fragment modified with cis-DDP at an r b level of 0.036 (see Example A) was incubated in the presence of increasing amounts of unlabeled 274-bp fragment modified with cis-DDP to the same extent. Binding reactions were done in triplicate for each level of competitor DNA. The amount of labeled platinated DNA bound to the protein was estimated by scintillation counting of the free and bound labeled DNA excised from dried gels. Cellular SSRP binding to the labeled 274-bp fragment platinated at 0.036 Pt/nucleotide was effectively competed by increasing quantities of unlabeled fragment modified to the same extent (lanes 6-20) . By contrast, unplatinated DNA did not compete with the labelled platinated DNA for binding of the cellular factor. Competition for binding was complete when a 100-fold excess of unlabelled platinated DNA was added to the binding reaction (lanes 18-20) . Binding of SSRP to labeled, platinated DNA was inhibited by 50% in the presence of a 3-fold excess of unlabeled platinated DNA. From these results, the affinity constant of the cis-DDP SSRP could be estimated. It was assumed that bands 1-3 observed in the autoradiograph represented one, two, and three bound protein molecules, repectively. DNA in the well of each lane was also asεumed to contain bound protein. From theεe data, the extent of inhibition of binding due to the competitor DNA could be calculated. The affinity conεtant was determined from the equation derived by Mϋller, R., Methods Enzvmol. 9:589-601 (1983): K = V 3 ([it]-[τ t ]) where [I,] represents the concentration of unlabeled platinated DNA that resultε in 50% inhibition of binding and [T,] repreεentε the concentration of labeled platinated DNA. The dissociation constant (K d ) is the reciprocal of the binding constant (K) . From the results of this competition study, K,, was estimated to be about 1 x 10 *,0 M. This estimate, which is a lower limit, was made by assuming one binding site for each molecule of DNA. Bands 2 and 3, however, suggest that more than one protein can bind per molecule of DNA. Both the radiolabeled and unlabelled competitor DNA fragments contained an average of 20 platinum adducts. Since the cis-DDP SSRP binds only to the l,2-d(GpG) and -d(ApG) adducts formed by cisplatin (see Example F) , comprising 90% of all platinum adducts of this drug, it was assumed that each molecule of competitor DNA contained about 18 potential binding siteε. When the concentrations of unlabelled and labelled binding εites were used in the above equation, the upper limit of the diεεociation constant was calculated to be 2 x 10' 9 M. The true value of the dissociation constant, therefore, lieε in the range of (1-20) x 10" 10 M. Of courεe, competition assays with purified protein and probes containing single, εite-εpecific platinum adductε can be uεed to determine the diεεociation conεtant more accurately. Example G: EMSA Study of the Selectivity Characteristics of the Cellular SSRP for cis-DDP DNA Adducts A more refined EMSA study was carried out to follow up on the results discuεsed in Example B. The 422 bp Aval DNA restriction fragment of M13mpl8 described in Example A was modified with various therapeutically active platinum compounds. HeLa extracts were prepared as described in Example A. Labelled, damaged DNA fragments were incubated in the absence of cell extract (-; lanes 1, 4, 7, 10, 13 and 16) , in the presence of HeLa cytosolic extract (S; lanes 2, 5, 8, 11, 14 and 17), or in the presence of HeLa nuclear extract (N; lanes 3, 6, 9, 12, 15 and 18). Samples were incubated and electrophoretically resolved aε described previously. Results obtained by gel mobility shift analysiε demonεtrated that the cellular SSRP bindε εelectively to DNA modified with cis-DDP, [Pt(en)Cl 2 ], and [Pt(dach)Cl 2 ], but not to DNA modified with either trans-DDP or [Pt(dien(Cl) ]C1. The latter two platinum compounds are unable to link adjacent nucleotides in DNA, whereaε the former three are known to form 1,2- intraεtrand d(ApG) and d(GpG) adductε. Example E: Further EMSA study of the Platinated DNA Structural Motif Recognized by the Cellular cis-DDP SSRP Conεtruction of Oligonucleotides Containing Specific Platinum-DNA Adducts. Oligonucleotides 22 baseε in length containing εingle 1,2-intraεtrand d(GpG) or d(ApG) or 1,3-intraεtrand d(GpTpG) adductε of cis-DDP, the 1,3-intrastrand d(GpTpG) adduct of trans- DDP, or the monofunctional N7-d(G) adduct of [Pt(NH 3 ) 2 (N3-cytosine) ] 2+ were prepared as previously reported. Rice et al . , Proc. Natl. Acad. Sci. USA 85:4158-4161 (1988) . These oligonucleotides are designated as "Top" strands. Unmodified Top εtrandε were also constructed as controls. Complementary oligonucleotides designated as "Bottom" strandε were conεtructed εuch that, when annealed to the adducted single-stranded fragments, they formed duplexes containing two-base 3'-overhangs at both ends. These synthetic, double-stranded oligonucleotides containing predefined types of platinum adducts are shown in Figure 1. The Bottom oligonucleotides were 5'-end labeled with [γ- PJATP (<3000 Ci/mmol, New England Nuclear) by polynucleotide kinase and purified from unincorporated ATP on a Nensorb-20 column (New England Nuclear) . Adducted and control Top oligonucleotides were 5'-end phosphorylated with nonradioactive ATP and also purified on Nensorb-20 columns. Top and Bottom strands were mixed at a mole ratio of 4:3, heated at 90°C, and then cooled slowly to 4°C to allow the two strands to anneal. High-concentration T4 DNA ligase (10,000 unitε/mL) was added, and the samples were incubated overnight at 13°C. Double- stranded oligonucleotides of 44, 66, 88 and 110 bp in length were then purified from native polyacrylamide gels according to the method of Maniatis (supra) . Theεe εynthetic duplex oligonucleotideε containing predefined, εpecifically placed platinated DNA εtructural motifε (εhown in Figure 1) were uεed aε damaged DNA fragments to investigate SSRP binding specificity in the competitive EMSA studieε. Substantial nonspecific binding to these oligonucleotides was observed, as evidenced by the presence of slower migrating bands seen in the cases where the oligonucleotides were not modified with platinum. Specific binding waε observed, however, to DNA fragments containing the 1,2-intrastand d(GpG) and d(ApG) cross-linked adducts of cis-DDP. SSRP bound to oligonucleotides 88 or 110 bp in length, but not to those that were 44 or 66 bp long. Thiε probe εize limitation presumably reflects a minimum requirement for a flanking nucleic acid domain in order for protein binding to occur. Binding was not observed with randomly modified DNA fragments at r b values of lesε than 0.007, suggesting that a minimum level of modification is required for binding of the DRP in crude extracts. The band representing specific binding to platinated oligonucleotides of 110 bp could be competed away with an about 340-fold excesε of unlabeled M13mpl8RF DNA modified with cis-DDP at a bound drug to nucleotide level of 0.041 but not with unlabeled unplatinated M13mpl8 DNA at the same approximately 340-fold excesε. No specific binding occurred in caεeε where the DNA probes contained the d(GpTpG) 1,3-intrastrand cross-linked adducts of cis- DDP and trans-DDP or the monofunctional d(G)-N7 adduct of {Pt(NH 3 ) 2 (N3-cytosine) }C1. Thuε, the reεultε of thiε εtudy further εupport the poεtulate that SSRP recognizeε a εtructural motif comprising a 1,2- intraεtrand dinucleotide adduct. Example I: EMSA Studies Revealed that the Cellular cis- DDP SSRP does not simply respond to ss DNA As noted previously in the Detailed Description, the 1,2-intrastrand d(GpG) and d(ApG) DNA adducts of cis-DDP bend the helix in the direction of the major groove, and are thought to produce a local region of ss DNA opposite to the site of the platinum lesion. In fact, such a ss motif could be detected by antinucleoside antibodies (reported by Sundquist et al .. Biochemistry 25:1520-1524 (1986)). This observation suggested that SSRP might recognize a single-stranded domain, rather than a structural motif (e.g., a helix kink) produced by the platinated DNA adduct itself. This possibility was excluded by a competitive EMSA study in which nuclear extracts from HeLa cells were incubated in the presence of 5000 cpm (0.2 ng) of the 274 bp ds restriction fragment described in Example A, modified with cis-DDP at 0.040 Pt/nucleotide. Single stranded DNA was prepared by boiling the unplatinated, radiolabeled 422 bp restriction fragment disclosed in Example A, and then allowing the DNA to reanneal in the presence of a 10-fold molar excesε of M13mpl8 circular ss DNA (+) strand. The 422 nucleotide (+) strand was then resolved on, and isolated from, a native polyacrylamide gel and platinated as described for the double stranded DNA fragments. Escalating concentrations (0.2-100 ng) of this unlabeled εε M12mpl8 DNA was added to EMSA samples as a competitor. Single-stranded DNA was not observed to compete with the cis-DDP modified dε DNA fragment for binding to SSRP, a reεult which bolsters the suggestion that SSRP does not simply reεpond to εε domainε. Example J: EMSA Studies Also Showed that the Cellular cis-DDP SSRP does not bind to UV-induced DNA lesions A factor has been reported in nuclear extracts prepared from HeLa cells that bindε εpecifically to DNA damage induced by UV irradiation. Chu, G. and E. Chang, Science 242:564-567 (1988). Accordingly, UV- damaged DNA fragmentε were prepared and employed in a competitive EMSA εtudy to determine whether the factor reported by Chu and Chang iε related to SSRP (see also Example F) . The 422-bp DNA fragment derived from Aval digestion of M13mpl8 (Example A) was purified by electrophoresis through a low-melting agarose gel followed by butanol extraction in the presence of CTAB. DNA fragments were labeled with [α- 32 P]dCTP and purified as described above. The labeled DNA fragments were then irradiated with a General Electric 15-W germicidal lamp (maximum output at 254 nm) calibrated with a UVX digital radiometer at a flux of 5 J/(m 2 -ε) and a final dose of 1500 J/m 2 . Competition reactions included the end-labeled, Pt-modified (r b of 0.038) 422 bp fragment, 10 μg of HeLa nuclear extract, and escalating levels (0.1-10 ng) of unlabelled competitor M13mpl8 DNA modified with either cis-DDP at an r b of 0.041, or with UV light as described in the preceeding paragraph. In a second series of competition reactions, end-labelled, UV- modified 422 bp fragment was used. The results of this study revealed that SSRP binding was not competed by a 1000-fold excess of M13mpl8RF DNA treated with UV at 1500 J/m 2 , which corresponds to a calculated level (Spivak et al . , Mutat. Res. 193:97-108 (1988)) of about 5.7 cyclobutane dimers per kilobase. Conversely, the binding of a factor found only in nuclear extracts to labelled DNA modified with UV light at 1500 J/m 2 could be competed with a 1000-fold excess of unlabeled, UV-irradiated M13mpl8 DNA, but not with a 1000-fold excess of DNA platinated with cis-DDP. These results bolster the conclusion that cis-DDP SSRP is not the factor described by Chu and Chang as capable of recognizing UV-induced DNA lesions. Example K: Partial Purification and Characterization of the Cellular cis-DDP SSRP Purification of Cellular cis-DDP SSRP. Saturated ammonium sulfate waε added dropwiεe to HeLa crude cytoεolic extractε to a final concentration of 40%. The mixture was stirred on ice for 30 minutes and centrifuged at 11,000 rpm in a Sorvall SM24 rotor for 30 minutes. Proteins present in the supernatant were precipitated with ammonium sulfate added as above to a final concentration of 65%. The 40-65% fraction (i.e., the second precipitate) was resuspended in buffer H (25 mM HEPES, pH 7.5, 150 mM KC1, 0.1 mM Na 2 EDTA, 1 mM DTT, and 10% glycerol) and dialyzed extensively against the same buffer. Sucrose Gradient Ultracentrifuoation. Essentially, the method of Johns, P. and D.R. Stanworth, J. Immunol. Methods 10:231-252 (1976) was followed. A portion of the 40-65% fraction representing 1 mg of protein was centrifuged through a 0-15% linear sucroεe gradient for 18 hourε at 43,600 rpm (ωt 2 = 1.34 x 10 12 , 170 OOOg) in a Beckman SW 50.1 rotor. Fractionε were removed from the top of the gradient and dialyzed extensively against buffer H. Each fraction was subεequently assayed for cis-DDP-DNA binding activity by EMSA, in the manner described in Example A (i.e., using the end-labelled, cis-DDP modified 422 bp Aval restriction fragment of M13mpl8) . Protein standards were centrifuged in parallel as molecular weight markerε. Fractions from this gradient were precipitated with methanol/chloroform (3:1 and reεuεpended in SDS loading dye (0.3 M Triε baεe, pH 9.0, 50% glycerol, 5% SDS, 5% 2-mercaptoethanol, 0.0025% brophenol blue). The fractionε were then electrophoreεed through a 12% SDS-polyacrylamide gel, and the gel was stained with Coomassie blue R-250 to detect protein. Figure 2 presents the results of this study to determine the size of the cellular cis-DDP SSRP by sucrose gradient sedimentation. The profile of the gradient is shown; EMSA study of the fractions revealed that SSRP was located in fractions 7-12, with the peak of activity in fraction 9. From these data, the sedimentation coefficient of SSRP was calculated to be 5.6S, which corresponds to an apparent molecular weight of 91000 daltons for a globular protein. It will be seen from the Exampleε which follow that this result is in agreement with assessments of the molecular weight of SSRP based upon modified Western blot analysis. Example L: Modified Western (Southwestern) Blotting Technique for Detecting the Presence of SSRP Preparation of Crude Extracts. Eukaryotic nuclear and cytosolic extracts of HeLa cells were prepared as described in Example A. Eεcherichia coli strain SG1161 (Ion") lysogenε were prepared aε described in the literature. Singh, H. et al .. Cell. 52:415-423 (1988). This strain of E. coli was chosen to reduce proteolytic degradation of the expressed fusion protein (comprising S-galactosidase and at least a portion of SSRP) . Radiolabelled and platinum-modified DNA fragments used for modified Weεtern Blotting εtudies were prepared as deεcribed in Example A. Southwestern Blot Procedure. Extracts were prepared from either IPTG-induced (IPTG refers to isopropyl-/S-D-thiogalactopyranoεide) lyεogenε or HeLa cells. Typically, 50 μg total protein per lane were separated by sodium doedecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) on an 8% εeparating gel and transferred onto nitrocellulose (Schleicher & Schuell, BA85, 0.45 μ ) according to conventional techniques. Following transfer, filters were processed as described in the literature. Laemmli, U.K., Nature . 227:680-685 (1970); Towbin, H. et al . , Proc. Natl. Acad. Sci.. USA. 76:4350-4354 (1979); Singh, H. et al .. Cell. 52:415-423 (1988) . To assay for DNA binding, nitrocellulose filter-bound proteins were incubated in binding buffer (30 mM HEPES [N-2-hydroxyethyl-piperazine-N-2-ethane- εulfonic acid NaOH] pH 7.5, 10 mM MgCl 2 , 2 mM MnCl 2 , 0.25% nonfat dry milk), uεing 20 mL per 20 x 20 cm filter, with 3 P-labeled DNA fragment (0.25-2.0 x 10 4 cpm/mL, lO *10 to 10 π M) . Poly(dΙ-dC)«poly(dI-dC) was added as competitor for non-specific DNA binding proteins at 10 μg/mL or 4 x 10 "s M. The incubations were run for 60 minutes at room temperature with gentle agitation. In an experiment using single stranded DNA as a probe, a mixture of 5 μg/mL each of Poly(dI- dC)«poly(dI-dC) and M13mpl8 single stranded (+ strand) DNA was used as competitor. Unbound DNA was then removed by washing the filters twice at 4°C with binding buffer lacking MgCl 2 and MnCl 2 . Thereafter, (damaged DNA fragment) : (protein) complexes present on the blot surface were detected by autoradiography with the use of an intensifying screen at -80°C. This procedure was used successfully to visualize HeLa cellular SSRP and recombinant fusion proteins having SSRP activity. The cellular protein was observed to have electrophoretic migration properties consiεtent with a globular protein of about 100 000 daltonε. These studies are more fully described below. Example M: Southwestern Blot Screening Procedures for Detection of Recombinant Expression Products having SSRP Activity Protein replica filters were prepared from an unamplified human B cell (RPMI 4265) cDNA library (Clontech Laboratories, Inc.) constructed in the expresεion vector λgtll. The cDNA library waε originally prepared by oligo(dT) priming of poly(A) + RNA, Chan. S.J. et al . , Proc. Natl. Acad. Sci.. US r 76:5036-5040 (1979). The library contains approximately 9 x 10 5 independent cloneε with inεert εizeε in the range of 0.73 to 4.1 kb and a titer of 3.6 x 10 9 plaque forming units (PFU)/mL. Screening of the λgtll recombinantε plated on E. coli hoεt strain Y1090 was carried out as described in Singh, H. et al .. Cell. 52:415-423 (1988), using cisplatin-modified, 32 P-labeled DNA to screen clones for platinated DNA binding. Each filter waε incubated for 60 inuteε at room temperature in 10 or 25 mL TNE (10 mM Tris-HCl pH 7.5, 50 mM NaCl, 1 mM Na 2 EDTA, 1 mM DTT) for 100 and 150 mm plates, respectively. The buffer contained -^P-labeled platinated DNA at a final concentration of approximately 3 x 10 4 cpm/mL (approximately 10" n M) as well as both sonicated native and denatured calf thymus DNA with an average length of approximately 1 kb at 1.0 and 5.0 μg/mL, reεpectively. The filterε were then waεhed at room temperature three times for ten minutes ' per wash using TNE, air dried, and autoradiographed at -80°C with the use of an intensifying screen for 24-48 hours. Putatively poεitive clones were rescreened for binding to cis-DDP-modified DNA. Secondary screenε were carried out on 100 mm plateε with plating mixtureε of approximately 5 x 10 3 PFU of phage, while tertiary screenε uεed plating mixtureε of about 100 PFU. Thiε protocol was employed succeεεfully to purify two recombinant phage, λPtl and λPt2, to homogeneity. Example N: Southwestern Blot Study of Cellular and Recombinant Proteins having SSRP Activity In order to demonstrate that the clones isolated in Example M encode proteins which specifically bind to DNA modified by cis-DDP, E. coli lysogens were prepared for each clone, as well as for the cloning vector lacking the insert. As a control, HeLa extract was also prepared and included in the analysis. Crude extracts obtained from induced lysogens were subjected to SDS-PAGE and the resolved proteins were transferred to nitrocellulose filters. Four filters were prepared, comprising the following samples: lane 1, HeLa cytosolic extract; lane 2, bacterial lysogen crude extract from the λgtll vector (lacking insert) ; lane 3, bacterial lysogen crude extract from λPt2; and lane 4, bacterial lysogen crude extract from λPtl. Following denaturation and renaturation according to the method of Celenza, J.L. and M. Carlson, Science. 233:1175-1180 (1986), the four filters were probed and developed aε follows: A, India Ink stain to visualize total proteins; B, a monoclonal antibody raiεed againεt 3-galactosidase, followed by immunoglobulin-specific detection according to the Weεtern Blotting method of Ausubel, F.M. et al . , Current Protocols in Molecular Biology, Green Publishing Associates and Wiley Interscience, New York, Section 10.7.1.; C, 3 P-labeled, unmodified 422 bp Aval restriction fragment of M13mpl8 (Example A) ; and D, the same DNA fragment modified with cis-DDP. Thus, filters C and D depicted the resultε of Southwestern blotting studies. These investigationε εhowed the preεence of two predominant polypeptideε in λPtl lysogens having S-galactosidase immunoreactivity, which selectively bind to DNA fragments modified by cis-DDP and not to the corresponding unmodified DNA fragments. These bands are separated by approximately 4 kDa. The slower migrating band correεpondε to a molecular weight of approximately 172 kDa. The faster migrating band can be attributed to proteolysiε of the phage encoded protein. In subsequent studies, filter-bound, electro¬ phoretically resolved proteins were also probed with DNA fragments modified with [Pt(en)Cl 2 ], trans-DDP, or [Pt(dien)Cl] + . These studies revealed that bacterial induced lysogens from λPt2 and λPtl bound only to DNA modified by cis-DDP or [Pt(en)Cl 2 ], in accord with results obtained with the HeLa cellular SSRP. The detection limit of this modified Western (Southwestern) Blot technique for binding of the phage-encoded proteinε to cis-DDP-modified DNA waε found to be approximately 2 platinum adductε per 100 nucleotides, corresponding to an r b level of 0.02. Example O: Restriction Enzyme Mapping of the Isolated cDNA Clones, λPtl and λPt2 Amplified phage stocks prepared from λPtl and λPt2 were used to isolate recombinant DNA. Maniatis, T. et al.. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp. 76-85 (1982) . Each clone was digested with a variety of restriction enzymes (obtained from International Biotechnologies and Bethesda Research Laboratories) . After electrophoretic separation, DNA fragments were transferred to a nitrocellulose filter. Id.. pp. 383- 386. To determine any homologies between the two cDNA clones, the filter was probed with λPt2 cDNA insert labelled with [α- 32 P]deoxy-cytidine triphosphate by the Klenow fragment of DNA poly eraεe I. Id.. pp. 113, 178. Hybridization was carried out with 10% dextran εulfate in 50% forma ide for 3 hours at 45°C, and the filterε were waεhed twice with 1 x SSC/0.1% SDS (wherein SSC iε 0.15 M NaCl, 15 mM triεodium citrate pH 7.0, and SDS iε εodium doedecyl εulfate) at room temperature followed by two additional waεheε with 0.1 x SSC/0.1% SDS at room temperature. Autoradiography was carried out at -80°C with use of an intensifying screen. The resultε of these studieε are summarized in Figure 3. Enzyme mapping analysis of the two recombinant phage λPtl and λPt2 indicated that they contain nucleotide sequences aligned at their 5' ends, with insert sizes of 1.44 and 1.88 kb, respectively. Southern blotting analysis confirmed homology between the two clones. The apparent molecular weight of the portion of the fusion protein encoded by λPt2 which repreεents the cloned human B cell polypeptide is estimated to be approximately 50 kDa. This polypeptide represents at least a portion of a cellular protein having cis-DDP SSRP activity. Example P Expression Studies of the Cellular Protein encoded by the λPtl and λPt2 Sequences Northern Blotting Technique. Cytoplasmic RNA from human HeLa, hamster V79, and murine leukemia L1210 cells were isolated by using a published procedure. Sonenshein, G. et al . , J. Exp. Med.. 148:301-312 (1978) . Twelve micrograms of RNA were loaded in each lane and resolved on a 1% agarose gel containing 6% formaldehyde, 20 mM 3-[N-morpholino] propanesulfonic acid, 5 mM εodium acetate and 1 mM Na 2 EDTA. RNA was transferred in 20 x SSC by capillary action to Gene Screen Plus™ brand blotting paper (New England Nuclear) . The λPt2 DNA inεert was labeled with [α- 32 P] deoxycytidine triphosphate according to a known technique. Feinberg, A.P. and B. Vogelstein, Anal. Biochem.. 132:6-13 (1983). The filter was probed with 10 6 cpm/mL of this probe in hybridization mixture (45% formamide, 10% dextran sulfate, 0.1% εodium phosphate, 50 mM Tris-HCl pH 7.5, 5x Denhardt's solution, 100 μg/mL sheared, denatured salmon sperm DNA and 0.5% sodium doedecyl sulfate) at 42°C. Thereafter, filters were waεhed twice uεing 2 x SSC at 65°C followed by two additional washings with 1 x SSC/0.1% SDS at 65°C. Autoradiography was carried out at -80°C with use of an intensifying screen. Preliminary Northern analysis of the expresεion of the λPt2 gene demonεtrated the presence of a conserved cytoplasmic RNA species of 2.8 kb in HeLa, murine leukemia L1210 and Chinese hamster V79 cells. The predicted molecular weight of the full length cellular protein encoded by this mRNA iε 100 000 daltons. It will be noted that this mass is similar to that of the binding factor identified as SSRP, aε observed by Southwestern blot analysis of HeLa cytosolic extracts. This correlation supportε the inference that the clone λPt2 encodeε a portion of thiε same factor. In a subsequent study, the following Northern blotting technique was employed to further characterize expression patterns of the SSRP gene: Northern Analvsiε. RNA was isolated by using standard procedures (Sambrook, J. , et al . , Molecular Cloning: A Laboratory Manual (1989) . Typically, 12 μg of RNA were used for electrophoretic analysis in 1% agarose gelε containing 6% formaldehyde, 20 mM MOPS, 5 mM NaOAc, and 1 mM EDTA. Gelε were denatured for 15 inuteε in 50 mM NaOH, 100 mM NaCl, neutralized in 100 mM Triε (pH 7.5), and tranεferred to GeneScreenPlus™ (New England Nuclear) by capillary action in 10X SSC. Filterε were rinsed in 2X SSC and baked in a vacuum oven for two hourε at 80°C. Pre-hybridization for four hourε and hybridization for 16 hourε with lxlO 6 cpm of labelled λPt2 DNA per ml of hybridization fluid waε carried out at 42°C in 30-40% formamide, 10% dextran εulfate, 0.1% NaPP,-, 50 mM Tris (pH 7.5), 5X Denhardt's, 0.5% SDS, and 100 μg/ml denatured εalmon εperm DNA. Filters were washed at 55°C with 2X SSC, 0.1% SDS twice, and in IX SSC, 0.1% SDS twice for 30 minutes each and exposed to X-ray film. In order to determine the tissue specificity of SSRP gene expression, total RNA was isolated from baboon brain, heart, ileum, jejunum, kidney, liver, muscle, and spleen tissue and subjected to Northern analysiε. The results of this survey revealed that the 2.8 kb SSRP message iε expressed in all tissueε examined. Rehybridization probing of the filter with a fragment of human 0-actin allowed normalization for RNA loading levelε, and εhowed that the relative levels of SSRP expression were εimilar each of the tissueε analyzed, except for brain tissue, in which it is higher. Becauεe of the exceptional εucceεε of ciεplatin in treating teεticular cancer, a more detailed analyεis of expresεion waε carried out in a εerieε of teεticular carcinoma cell lines. Several bladder cancer cell lines (Maεters, J.R.W. Cancer Res. 46:3630-3636 (1986)) were studied concurrently because cisplatin is less active against this type of cancer. SSRP is expresεed in all of the bladder and testicular cell lineε examined; no general trends were apparent. These data indicate that the intracellular level of SSRP mRNA does not correlate with the antitumor activity of cisplatin for a particular tissue type. Since the protein described herein specifically recognizes DNA adductε of active antitumor platinum complexes, its possible role in acquired resiεtance of cells to cisplatin was also investigated. A Northern blot analysiε in which the λPt2 clone waε used to probe cytoplasmic RNA levelε in a εerieε of ciεplatin resistant human, mouse, and hamster cell lines was carried out. Data obtained from this study indicate that the level of SSRP expression does not correlate with resiεtance in theεe cell lines. In order to study whether expression of the cisplatin-DNA SSRP could be induced in cells treated with the drug, cytoplasmic RNA was isolated from HeLa cells which had been exposed to a range of concentrations of cisplatin. The 2.8 kb mRNA SSRP gene transcript was not inducible by a wide range of cisplatin concentrations over the course of 48 hours. Example Q use of Clones λPtl and λPt2 to Obtain the Full Length human cDNA Sequence Encoding SSRP Labelling of Probes for Hybridization. The λPt2 clone (reported in Toney, J.H. et al . , Proc. Natl. Acad. Sci. , USA 86:8328-8332 (1989)) was used as a probe for hybridization and library screening. λPt2 was radiolabelled by random oligonucleotide priming as described in Feinberg, A.P. and Vogelεtein, B. Anal. Biochem 132:6-13 (1983). Typically, 50-100 ng of DNA in low melting point agaroεe waε boiled, primed with pd(N) 6 oligonucleotideε (Pharmacia), and labelled with α-[ 32 P]dCTP by Eεcherichia coli DNA polymeraεe I (Klenow fragment) . Labelled fragmentε were purified by εpin dialyεiε over Spehadex G-50 columnε and the extent of incorporation of radioactivity waε monitored by scintillation counting. Library Screening. For the primary screen of each cDNA library, 5x10 6 recombinant phage were plated on E. coli host strain Y1088. Duplicate replica nitrocellulose filters were prepared and then denatured (0.5 M NaOH, 1.5 M NaCl) , neutralized (1 M Triε (pH 7.4), 1.5 M NaCl) , and rinεed with 2X SSC (20X SSC: 3 M NaCl, 0.3 M Na 3 C 6 H 5 0 7 ) . After baking for two hours at 80°C in a vacuum oven the filters were pre-incubated at 42°C for four hours with hybridization fluid (50% formamide, 1M NaCl, 50 mM Tris (pH 7.5), 0.5% SDS, 10% dextran sulfate, IX Denhardt'ε solution, and 1 mg/ml denatured salmon sperm DNA) . Probe was then added at a concentration of lxl0 6 cpm of labeled DNA per ml of hybridization fluid and the incubation was continued for an additional 16 hours. The filters were washed once at room temperature in 2X SSC/0.1% SDS, twice at 65°C in 2X SSC/0.1% SDS, and twice at 65°C in 0.1X SSC/0.1% SDS for fifteen minutes each. The filters were air dried briefly and analyzed by autoradiography. Multiple rounds of screening were used to isolate plaque pure bacteriophage clones. Single plaques were amplified in liquid culture for DNA preparation and further analysis. In this manner, overlapping cDNA clones spanning the entire coding sequence of the human SSRP gene were identified and isolated from human embryonic kidney (HEK) fetal muscle (M) , and baεal ganglia (BG) cDNA libraries. These clones were subjected to Southern blot and sequencing analyses as described below. Example R Southern Blotting Studies of Overlapping cDNAs Encoding Human SSRP Southern Analysis. High molecular weight genomic DNA was prepared by slowly dripping cells into lysis buffer (10 mM Tris (pH 8.0), 100 mM NaCl, 1 mM EDTA, 1% SDS).,- followed by overnight digestion with proteinase K (100 μg/ml) , multiple phenol and chloroform extractions, and resuεpenεion in TE (50 mM Triε (pH 7.5), 10 mM EDTA). For each sample, 10 μg of DNA was digested to completion and the fragments separated by electrophoresis in 0.8% agarose gels. Gels were denatured for 45 minutes (0.5 M NaOH, 1.5 M NaCl), neutralized for 60 minutes (l M Tris (pH 7.4), 1.5 M NaCl) and the DNA immobilized on Zetabind™ membrane (Cuno) by capillary tranεfer for 16 hours in 10X SSC. After rinsing the filter with 2X SSC, it was baked in a vacuum oven at 80°C for two hours. Following pretreatment at 65 β C for one hour (0.5X SSC, 0.5% SDS) the filters were hybridized and washed as described above for library screening, and then analyzed by autoradiography. A schematic representation showing the relationship between human cDNA clones encoding SSRP iε preεented in Figure 4. Cloneε λPtl and λPt2 were iεolated from a human B cell library aε diεcuεsed previously. Clone HEK 402 was isolated from a human embryonic kidney library, and contains the complete SSRP cDNA sequence and polyadenylation signal. Clone M 801 was iεolated from a fetal muεcle library, and lackε the 3' end of the gene but containε 147 baεeε of additional 5' untranεlated εequence. Clone BG 801 was iεolated from a basal ganglia cDNA library and alεo lackε the 3' end of the gene, but εerved to confirm the εequence of itε 5' end. All cDNA cloneε were completely εequenced in both directionε aε deεcribed in the following Example, and were found to be identical in overlapping regions. Example S Sequencing of Human cDNAs Encoding SSRP and Characterization Thereof Subcloning. Purified phage DNA was digested with EcoRI to release the cDNA inserts. The EcoRI fragments were isolated from low melting point agarose gelε uεing GENECLEAN™ (Bio 101) and ligated into the EcoRI site of plasmid pBlueεcript SKII+. After tranεformation of competent E. coli XL-1 cells, single colonies were isolated and amplified in liquid culture. DNA was purified by using Qiagen affinity chromatography. Secruence Determination and Analysis. Sequence determination was performed on double-stranded plasmid DNA by using the chain termination method (Sanger, F. , et al . , Proc. Natl. Acad. Sci.. USA 74:5463-5467 (1977)) and Sequenase T7 DNA polymerase (United Stateε Biochemical) . Sequence analysis employed software from Genetics Computer Group (GCG) at the University of Wisconsin (Devereaux, J., et al . , Nucl. Acids. Res. 12:387-395 (1984)). Homology εearcheε were made by uεing the BLAST Network Service at the National Center for Biotechnology Information (Altεchul, S.F. et al . , J. Mol. Biol. 215:403-410 (1990)). By uεing the εequence information from theεe clones, a composite human sequence representing 2839 bases of DNA was generated. This sequence is shown in Figure 5; it contains a continuous open reading frame of 2130 baεeε beginning at poεition 275. The sequence surrounding the methionine start codon conforms well with the initiation εites of other vertebrate cDNAs (Kozak, M. Nucl. Acids. Res. 15:8125-8132 (1987)) and is conserved in homologs isolated from mouse (Shirakata, M. et al . , Molecular and Cellular Biology 11:4528-4536 (1991)) and Drosophila melanogaεter (Bruhn, S., et al . , Prog. Inorg. Chem. 38:477-516 (1990)). A consensus polyadenylation signal AATAAA is present within the 435 bases of 3' untranslated sequence beginning at position 2800. The εequence predictε a 710 amino acid protein of molecular weight 81,068 Daltons, also shown in Figure 5. The amino acid composition reveals a strikingly high percentage of charged residueε (36%) . Further analyεiε of the protein εequence indicated the preεence of εeveral highly charged domains, illustrated in Figure 6. There is an acidic domain, aa 440-496, which contains 26 negatively charged and 4 positively charged amino acids. Two basic domains, denoted Basic I and Basic II, are located at aa 512-534 and aa 623-640, respectively. At the carboxyl terminuε of the protein, aa 661-709, there iε another highly charged εerieε of amino acids containing 14 negative and 9 poεitive reεidueε. Analysis of the hydropathy profile shows the entire region from aa 400 to the carboxyl terminus of the protein to be highly hydrophilic (not shown) . A search of protein data baseε with the predicted amino acid εequence revealed εome interesting homologieε. SSRP εhowed the greateεt homology to high mobility group (HMG) 1 and 2 proteinε from εeveral εpecieε, (Eink, L. and Buεtin, M. Exp. Cell Reε. 156:295-310 (1985); Buεtin, M. , et al . , Biochim. Biophvs. Acta 1049:231-243 (1990)) and to a transcription factor containing HMG-box domains, hUBF (Jantzen, H.M., et al .. Nature 344:830-836 (1990)). The location of the HMG box is indicated in Figure 6. Optimal alignment of human cisplatin-DNA SSRP with human HMG1 revealing 47% identity in the regions compared. Homology was also found between SSRP and other HMG-box proteins which have been recently reported. See Jantzen, H.M., et al . , Nature 344:830- 836 (1990); Sinclair, A.H. , et al . , Nature 346:240-244 (1990); Gubbay, J. , et al . , Nature 346:245-250 (1990); Pariεi, M.A. & Clayton, D.A. Science 25:965-968 (1991); Travis, A., et al . , Genes & Dev. 5:880-894 (1991); Waterman, M.L. et al . , Genes & Dev. 5:656-669 (1991); Diffley, J.F. et al . , Proc. Natl. Acad. Sci. USA 88:7864-7868 (1991). It is important to note, however, that no obvious consenεuε HMG-box sequence emerges from εuch a compariεon. In addition, the acidic region of SSRP haε limited homology to nucleolin, (Srivastava, M. , et al . , FEBS Lett. 250:99-105 (1989)) which is involved in transcriptional control of rRNA genes. The human map position of the SSRP was also determined, using a panel of human chromosome-specific human-rodent hybrids. Initial experiments placed the gene on chromoεome 11. Further refinement with a serieε of hybrid cell lines containing only small defined segmentε of human chromosome 11 on a rodent genomic background (Glaser, T. Ph.D. dissertation, Massachusetts Institute of Technology (1989)) localized the position of the clone to llql2. Placement of the sequence on the long arm of human chromoεome 11 iε particularly intereεting because the murine homolog to SSRP has been mapped to mouse chromosome 2 (Shirakata, M., et al . , Molecular and Cellular Biology 11:4528-4536 (1991)). Previously, a syntonic relationεhip had been demonεtrated only for mouse chromoεome 2 and human chromosome lip (Nadeau, J.H., et al . , Mamm. Genome l:S461-S515 (1991)). Example T Use of the human cDNA Clone λPt2 to Obtain the Full Length Drosophila melanogaεter homolog of human SSRP In view of the expression pattern and evolutionary conservation of the SSRP gene, indicating a protein with an in vivo role important for normal biological functions, at least one SSRP homolog from a lower species was desired in order to further delineate conserved domains likely to be critical for SSRP function. Accordingly, a D . melanogaεter head cDNA library was screened using the human cDNA clone λPt2 (radiolabelled as described in Example O) , under low stringency conditions according to the following procedure: Library Screening. For the primary screen of the Droεophila head cDNA library (N. Itoh, et al . , Proc. Natl. Acad. Sci. USA 83:4081 (1986)), 5xl0 6 recombinant phage were plated on E. coli host strain Y1088. Duplicate replica nitrocellulose filters were prepared and subsequently denatured (0.5 M NaOH, 1.5 M NaCl), neutralized (1 M Tris (pH 7.4), 1.5 M NaCl), and rinsed with 2X SSC (20 X SSC: 3 M NaCl, 0.3 M Na 3 Cf_ 5 0 7 ) . Baking for two hours at 80°C in a vacuum oven was followed by pre-incubation at 42°C for 4 hourε with hybridization fluid (30% formamide, IM NaCl, 50 mM Tris (pH 7.5), 0.5% SDS, 10% Dextran Sulfate, IX Denhardt'ε, and 1 mg/ml denatured salmon sperm DNA) . Labelled λPt2 probe was added to a final concentration of 1x10* cpm of labelled DNA per ml of hybridization fluid and incubation continued for 16 hours. The filters were waεhed once at room temperature in 2X SSC/0.1% SDS, twice at 55°C in 2X SSC/0.1% SDS, and twice at 55°C in IX SSC/0.1% SDS for fifteen minuteε each. After the waεhing waε completed the filterε were air dried briefly and analyzed by autoradiography. Plaque pure bacteriophage cloneε were iεolated by multiple rounds of screening. Single plaques were amplified in liquid culture for DNA preparation and further analyεiε. Ten Droεophila cDNA cloneε were identified, with varying degrees of hybridization to the human cDNA. These bacteriophage clones were isolated and purified through successive rounds of screening. Two of these, denoted DM 3002 and DM 1001, were chosen for further study based on their strong hybridization to the human clone and their large size relative to other clones. Restriction and sequence analyses of these clones is deεcribed in the Exampleε which follow. Example U Southern Blotting Analysis of Overlapping cDNAs Encoding Drosophila SSRP Southern Analysis. DNA from each specieε (human and fly) waε digested to completion with EcoRI and the fragments were separated by electrophoresis in 0.8% agaroεe gels. The gel was then denatured for 45 minutes (0.5 M NaOH, 1.5 M NaCl), neutralized for 60 minutes (1 M Tris (pH 7.4), 1.5 M NaCl) and the DNA transferred to Zetabind™ membrane (Cuno) by capillary action for 16 hours in 10X SSC. After rinsing the filter with 2X SSC, it was baked in a vacuum oven at 80°C for 2 hours. Following pretreatment at 65°C for one hour (0.5X SSC, 0.5% SDS), the filters were hybridized and washed aε deεcribed above for library screening. EcoRI digeεtion of the bacteriophage cloneε, DM 3002 and DM 1001, with EcoRI releaεed a 2.3 kb inεert from DM 3002, and two fragmentε of εize 1.4 and 1.8 kb from clone DM 1001. Theεe three fragmentε were gel purified, εubcloned individually and εubjected to sequence analysiε (described below) , as well as reεtriction endonucleaεe mapping. Sequence analysis of the three subcloned fragments confirmed that there was significant overlap between DM 3002 and the 1.8 kb EcoRI fragment of DM 1001. Northern analysiε of the two EcoRI fragmentε of DM 1001 indicated that the 1.4 kb fragment recognized two head-εpecific RNA εpecieε of 3.5 and 1.6 kb. However, rehybridization of this blot with the 1.8 kb EcoRI fragment revealed that these RNA species were not recognized by this portion of the clone, indicating that clone DM 1001 was a chimera. Therefore, the 1.4 kb EcoRI fragment was not considered further. Figure 15 shows the alignment of clones DM 3002 and the 1.8 kb EcoRI fragment of DM 1001. Example V Sequencing of Droεophila cDNAs Encoding SSRP and Characterization Thereof Subcloning and sequencing of the D . melanogaεter cDNA sequences was carried out essentially as described above in Example S. Clones DM 3002 and 1001 were sequenced completely in both directions; as noted above, significant overlap between DM 3002 and the 1.8 kb EcoRI fragment of DM 1001 was observed. The sequences of clones DM 3002 and the 1.8 kb fragment of DM 1001 were combined to create a composite εequence of 2384 bases, εhown in Figure 8. Intereεtingly, there are large open reading frameε in both directionε from baεeε 123-2291 and from bases 2300-600. The larger of the two open reading frameε predicts a 723 amino acid protein of molecular weight 81524 daltons, the sequence of which is alεo εhown in Figure 8. Thiε εequence εhowε extenεive homology to the human structure specific recognition protein, the cDNA of which was used as a probe. For this reason, the 81 kD protein was assumed to be the correct reading frame. The AUG codon at position 123 of this open reading frame iε believed to be the true εtart εite, both becauεe there iε an in-frame εtop codon upstream from this site and because the start εite iε the εa e aε for the human protein. No conεenεus polyadenylation signal is seen within the 93 baseε of 5' untranεlated sequence. It seemε clear, however, that the complete coding εequence of the Droεophila homolog of human ciε- DDP SSRP iε contained within the cloneε sequenced. The homology at the nucleotide level between the human and Droεophila cDNAs iε 54%, and thiε εimilarity iε confined mainly to the coding regionε of the sequences. The homology in the 5' and 3' untranslated regions is 32% and 37%, respectively, whereas the predicted amino acid sequenceε of the two εpecies SSRPs share 53% identity and 72% similarity at the amino acid level over their entire length. Moreover, the sizes of the two SSRPs are quite comparable, and both contain a large number of charged amino acids (36% for the human protein and 38% for the Droεophila protein) . However, the Droεophila protein is more acidic than the human protein with an isoelectric point of 5.40. Both proteins have their charged residueε concentrated within small discrete regions, and these domains are conserved, depicted schematically in Figure 9. A search of the PROSITE database revealed one potential glycosylation εite and eeveral potential phosphorylation siteε which are conεerved between theεe proteinε. An asparagine residue which fits the consenεuε for glycoεylation (R.D. Marshall, Ann. Rev. Biochem.. 41:673 (1972)) is at position 567 in the Droεophila protein and at position 559 in the human protein. At position 324 in both proteinε there iε a conserved threonine residue with the two required amino terminal baεic reεidueε which iε potentially phoεphorylated by cyclic AMP-dependent protein kinase (J.R. Feramisco, et al . , J. Bio. Chem.. 255:4240 (1980); D.B. Glasε, et al . , Bio. Chem.. 261:2987 (1986) ) . Also conserved are five siteε conεiεting of a serine residue with an amino acid at the +3 position which fitε the conεenεuε εequence for phophorylation by casein kinase II (O. Marin, et al . , Eur. J. Biochem.. 160:230 (1986); E.A. Kuenzel, et al . , J. Bio. Chem.. 262:9136 (1987)). These serineε are at poεitions 80 and 399 in both proteins, and at positionε 443, 472 and 670 in the Droεophila protein, equivalent to positionε 444, 474, and 672 in the human protein. Protein kinaεe C requireε a baεic amino acid two poεitionε away from the phoεphorylated εerine or threonine residue on the carboxy terminal side of the protein (A. Kiεhimoto, et al . , J. Bio. Chem.. 260:12492 (1985); J.R. Woodgett, et al . , Eur. J. Biochem.. 161:177 (1986)). There are seven such sites conserved between these proteins at positionε 37, 111, 141, 209, 344, and 385 in both proteinε and at poεition 636 in the Drosophila protein, equivalent to poεition 627 in the human protein. Uεing the BLAST Network Service at the National Center for Biotechnology Information (S.F. Altschul, i s . Mol. Biol. f 215:403 (1990)), a nonredundant search of protein databases with the predicted Drosophila amino acid εequence revealed homologies conεiεtent with the human protein. The DNA structure-εpecific recognition protein εhowed homology to HMG-l and -2 proteinε from εeveral species, and to a transcription factor protein (hUBF) which contains an HMG box. As was found for the human protein sequence, the highly charged domains of the protein proved to be homologous to highly charged domains of other proteins, especially the transcriptional regulator nucleolin. Computer analysiε for the presence of potential structural domains was also carried out. For both the human protein and its Droεophila homolog, Chou and Fasman analysiε of hydropathy (P.Y. Chou and G.D. Fasman, Biochem.. 13:211 (1974); (P.Y. Chou, and G.D. Fasman, Ann. Rev. Biochem.. 47:251 (1978) predicts the entire carboxy terminal half of the proteinε, from aa 400 to the end, to be highly hydrophilic. No major regionε of amphiphilicity are apparent in either protein. Comparison of secondary structural predictionε for the human protein and itε Drosophila homolog reveal a number of regionε that appear to be helical in both proteinε when analyzed either with the method of Chou and Faεman (P.Y. Chou and G.D. Fasman, Biochem.. 13:211 (1974); (P.Y. Chou and G.D. Fasman, Ann. Rev. Biochem.. 47:251 (1978) or with the method of Robson and Gamier (B. Robεon and E. Suzuki, j. Mol. Biol. 107:327 (1976); (J. Gamier, et al . , J. Mol. Biol. 120:97 (1978)). Specifically, these regions surround approximately aa75-105, 150-165, 290-300, 405- 425, 450-465, 480-495, 525-540, 580-620, and 675-690. Example W In situ Hybridization Studies of the Drosophila SSRP βene Jn situ Hybridization to Polvtene Chromosomes. Polytene chromosomes were prepared from the salivary glands of third instar larvae as described previously (M. Aεhburner, prosophila: A Laboratory Manual pp. 37- 47 (1989)). Nick translation of plasmid DNA containing clone DM 3002 with biotinylated-16-dUTP (ENZO Diagnostics) , detection with Streptavidin-biotinylated peroxidase (Detek-1-HRP, ENZO Diagnoεticε) , and hybridization steps were all performed with standard techniques (M. Ashbumer, Droεophila: A Laboratory Manual pp. 37-47 (1989)). The reεults of thiε εtudy placed the Droεophila clone on the right arm of chromosome 2, in band 60A 1- 4. Deficiencies in this region, εpecifically from 59D4-5; 50A1-2 and 59D8-11; 60A7 produce maternal effect mutationε that are female εterileε (T. Schupbach and E. Weischaus, Genetics. 121:101 (1989)). Interestingly, the egalitarian gene which also mapε to the region, iε required for oocyte differentiation (P.F. Lasko and M. Ashburner, Genes and Dev.. 4:905 (1990)). Other mutants which map to the region include abbreviated and forkoid, which affect bristle formation, and lanceloate , which elongates the wing (Diaz-Benjumea and A. Garcia-Bellido, Roux s Arch. Dev. Biol. , 198:336 (1990)). The Droεophila guanine nucleotide-binding protein G,α, also maps to position 60A on polytene chromoεomeε (F. Quan, et al . , Proc. Natl. Acad. Sci. USA 86:4321 (1989)). Recently, a member of the transforming growth factor- / ? family, denoted the 60A gene, has also been mapped to this region. K.A. Wharton, et al . , submitted for publication. Example Y EMSA and Modi ied Western Blotting Studies of Yeast Cell Extracts Purification of Pt-DNA mobility shift activity. Yeast cells (BJ 296) were grown to late log phase (O.D. 0.8) in 6 L YPD and harvested by centrifugation for 15 minutes at 5000 g. The yield was 60 G wet cells. The pellet was washed once with water and resuspended in 180 mL TM (50 mM Tris-HCl (pH 8) 12.5 mM MgCl 2 , 1 mM EDTA, ImM DTT and 20% glycerol) buffer containing 0.1 M KCl, 100 mM PMSF, lOmg/ml leupeptin and lmg/mL pepstatin. After two paεεageε through a french preεε at 24,000 pεi the lysate was cleared of debris by centrifugation at 14,000 g for 5 minutes. Ammonium εulfate (15.2 g, 25% saturation) waε added to the supernatant (190 mL) and the solution waε εtirred for 30 minuteε on ice. Following centrifugation at 14,000 g for 10 minuteε, ammonium εulfate (34.2 g, 55% saturation) was added. The precipitated proteins were collected by centrifugation, disεolved in TM buffer 0.1 M KCl, 1 mM PMSF and desalted on a Biorad P-6 size- excluεion column. The reεulting εolution waε loaded onto either a DEAE-εepharoεe or a S-sepharose column. The columns were washed with TM buffer, 0.1 M KCl and eluted with a TM buffer 0.1 to 1.0 M KCl gradient. Bandshift active fractions from these columns were diluted to 0.1 M KCl with TM buffer, loaded onto a heparin fast-flow column (BioRad) and eluted with a 0.1-1.0 M KCl gradient. Bandshift assay (EMSA) . 15 μL aliquots of selected fractions from the column chromatography were mixed in solutions containing 10 mM Tris-HCl 10 mM NaCl, 0.5 mM EDTA, ImM DTT and 20% glycerol, 0.2 μg/mL poly(dldC) and 1000 cpm of a [ 32 P] end-labeled 123 bp DNA fragment. For platinated samples, the ratio of cis-DDP/nucleotide was 0.021. The reactions were incubated at 25°C for 15 minutes, loaded onto 8% TBE polyacrylamide gels and electrophoresed at 4°C. Dried gels were exposed to Kodax X-AR film. Bandshift activity was quantified using a Molecular Dynamics phosphor-imager. Modified Weεtern Analyεis. Proteins were resolved on SDS-polyacrylamide gels and electroblotted to nitrocelluloεe filters. The filterε were treated with blotto (50 mM Tris HCI pH 7.5, 50 mM NaCl, 1 mM EDTA, 5% nonfat dry milk powder) for 1 hour, washed twice for 10 minutes with TNE 50 (10 mM Triε pH 7.5, 50 mM NaCl, mM EDTA, 1 mM DTT) and denatured (50 mM Triε HCI pH 8.0, 7 M guanidine HCI, 1 mM EDTA, 50 mM DTT, and 5% (v/v) blotto) for 1 hour. Following overnight renaturation (50 mM Triε HCI pH 8.0, 50 mM NaCl, 1 mM EDTA, 2 mM DTT, 0.1% Nonidet P-40 and 5% (v/v) blotto) the filters were washed with 5% dry milk in 20 mM HEPES pH 7.5. The filters were incubated for two hourε in 30 mM HEPES, 10 mM MgCl 2 , 0.25% dry milk, 20 μg/mL poly(dIdC)»poly(dIdC) and 1 x 10 6 cpm/mL [ 32 P] end- labeled probe. Exceεε probe was removed by washing the filters twice for 10 minutes at 4°C with a 30 mM HEPES, 0.25% dry milk solution. In an initial experiment to determine conditions required to purify the yeast SSRP protein(s), (NH 4 ) 2 S0 4 waε added to 25%, 40% and 60% εaturation. The proteins precipitating at the various (NH 4 ) 2 S0 4 concentrations were analyzed by modified Western (i.e., Southwestern) blotting, and corroborated by EMSA. As asεessed by Southweεtem blot, an 82 000 dalton protein iε preεent in the yeaεt whole cell extract, waε well aε in the 0- 25%, 25-40% and 40-60% (NH 4 ) 2 S0 4 saturation fractions. This band is apparently absent from the supernatant. In addition, a rather large protein, -190 kDa, came down in the clearing spin, preceding the (NH 4 ) 2 S0 4 precipitations. A parallel blot was probed with unmodified DNA; no DNA binding was observed on it. EMSA analyεiε of the εame εampleε showed that the 40- 60% fraction apparently contains the highest mobility- shift activity, but activity is also present in the 25- 40% fraction and the supernatant. Further purification of the bandshift activity was achieved with S-sepharoεe chromatography. In one preparation, the 25-60% proteinε were redissolved, deεalted by dialysis or gel filtration, loaded onto a S-sepharoεe column, and eluted with a 0.1-1.0 M KCl gradient. It waε found that bandεhift activity elutes in two peaks with a complex pattern of shifted probe. Samples of the fractions representing the peaks of activity by EMSA were pooled and subjected to modified Western blotting. This study εhowed an enrichment of two proteinε having electrophoretic mobilitieε conεistent with masses of 42 000 and 40 000 daltons. Example Z EMSA and Modified Western Blotting Studies of the Polypeptide Encoded by Yeast SSRP Clone λyPt Fusion Protein Preparation. Stable lysogens of λyPt and λgtll were prepared in Y1090 E. coli cells. Lysogenε were grown in LB at 32°C to OD 0.5 when the temperature waε εhifted to 42°C for 20 minuteε. The β- galactosidase fusion protein was induced by adding to IPTG (10 mM) . Two methodε were uεed to harveεt total protein: Method A, cellε were harveεted 1 hour after IPTG induction, by centrifugation and resuspended in 0.01 volumeε of TM buffer containing 100 mM PMSF and flash frozen in liquid nitrogen; Method B, 2.0 mL aliquots were harvested by centrifugation at 10 minutes intervals following the IPTG treatment, resuεpended in SDS-PAGE loading buffer, placed in boiling water for 5 minuteε and εtored at -80°C. Cell debriε waε removed by centrifugation from samples prepared by either method immediately prior to SDS-polyacrylamide gel electrophoreεiε. The fusion protein produced by the lysogen of λyPt in Y1090 is capable of binding cis-DDP modified DNA on a modified Western blot (using essentially the same procedure as discussed in the preceeding Example) . The fusion protein waε obεerved to have an electrophoretic mobility consistent with a protein of 180 000 daltons. Since the S-galactosidase portion of this polypeptide accounts for 113 000 daltons, the remaining 63 000 daltons is the expression product of the cloned gene. It should be noted that this fusion protein haε proven to have uncertain εtability (i.e.. Southwestern blotting revealε the preεence of multiple reactive bandε, presumably arising from proteolysis) . Example AA Subcloning, Sequencing and Sequence Characterization of Yeast SSRP Clone λyPt Subcloning and DNA Sequencing. The 1.7, 1.1 and 0.6 kB EcoRI fragments from λyPt were ligated into the EcoRI site of pBluescript IISK + yielding plaεmids pSBl, pSB2 and pSB3, respectively. Plasmid DNA waε alkaline denatured for the εequencing reactionε. Double- stranded λyPt DNA waε prepared for sequencing by Sad digestion and treatment with T7 gene 6 exonuclease to produce a single-stranded DNA template. Sequencing was performed by the dideoxy chain termination method using sequenaεe T7 DNA polymerase (US Biochemical Corp.). Sequence fragments were assembled using the GCG program. (Devereux, Haberli, et al . , (1984) Nucleic Acids Research 12(l) :387-395. Nonredundant searches or protein and DNA sequence databases were performed with the BLAST network service provided by the National Center for Biotechnology Information (NCBI) . Complete sequencing of λyPt waε achieved by sequencing the three subcloned EcoRI fragmentε identified above. Since EcoRI digeεtionε of λyPt DNA releaεeε three fragmentε, the cloned DNA apparently containε two internal EcoRI εites (See Figure 10; further details are given below) . The yeast genomic DNA contained in λyPt was found to total 3292 bases the εequence of which is shown in Figure 11. An open reading frame, contiguous with the reading frame for the /S-galactosidase gene of lamda phage, is found in the λyPt DNA sequence. This reading frame extends from bases 1 to 1626 and is shown in Figure 12. The hexanucleotide polyadenylation signal, AATAAA, found at nucleotides 1632-1637, is preεent in approximately 50% of S. cerevisiae geneε (Hyman, L. , S.H. Seiler et al . , (1991) Mol. Cell. Biol. 11(4) :2004-2012) . Tranεlation of the open reading frame found in clone λyPt yieldε an amino acid εequence of 534 reεidues. This peptide sequence is herein referred to as fySSRP, for fractional yeast structure specific recognition protein. Examination of the amino acid sequence of fySSRP reveals a εtriking feature: there are eight runs of five or more glutamines, of which the longeεt is fifteen. In all, there are 110 glutamine residues, or one fifth of the total. Fifty asparagine reεidueε account for another 9.2% of the amino acidε. Example BB Expression of the Yeast SSRP Gene Probe Preparation. The 0.6, 1.1 or 1.7 Kb EcoRI fragments from pSBl, pSB2 or pSB3 were used as templates for probe preparation. Approximately 0.2 μg of DNA in low melting point agarose was boiled with 0.1 μg d(N) β oligonucleotides (New England Biolabs) , and labeled with α-[ 32 P]dCTP by E. coli DNA polymerase I (Klenow fragment) . Reactions were stopped by extraction with phenol/chloroform. Northern Analysis. Total yeast RNA was prepared by the published procedure. (Kohrer, K. and H. Domdey (1991) Guide to Yeast Genetics San Diego, Academic Presε Inc. 398-405). RNA MW markerε (BRL Inc.) and 10 μg total yeast RNA were subjected to electrophoretic analysiε in 0.8% agarose gels containing 6% formaldehyde, 20 mM MOPS, 5 mM NaOAc, and 1 mM EDTA. Gels were denatured for 15 mins. in 50 mM NaOH, 100 mM NaCl, neutralized in 100 mM Tris (pH 7.5), and transferred to nitrocellulose by capillary action in 2OX SSC. Filters were baked for two hrs. at 80°C. The filter waε prehybridized (50% formamide, 0.1% NaP0 4 , 50 mM Tris (pH 7.5), 5X Denhardt's εolution, 0.5% SDS, and 100 μg/ml denatured εalmon εperm DNA) for four hourε at 42°C and hybridized overnight in prehybridization εolution containing 10% dextran εulfate and with lxlO 6 cpm/mL of labeled DNA probe. Filterε were waεhed at 55°C twice for 30 mins. with 2X SSC, 0.1% SDS twice, and in IX SSC, 0.1% SDS and exposed to X-ray film. Northern blotting analysis establiεhed that ySSRP iε encoded by a 2.1 kb mRNA εpecieε. Example CC Southern Blotting Studies of Clone λyPt Southern Analysis. Typically, 10 μg of genomic yeast DNA or lamda DNA were treated with restriction enzymeε and the fragments resolved by electrophoresis on 0.8% agarose gels. Gels were treated with 0.2 N HCI for 10 min., denatured for 20 minutes (0.5 M NaOH, 1.5 M NaCl) , and neutralized for 40 minutes with two changes of 1 M Triε pH 7.5, 1.5 M NaCl. The DNA waε tranεferred to nitrocelluloεe filterε (Schleicher and Schuell) by capillary tranεfer overnight with 2OX SSC (i.e., 3 M NaCl, 0.3 M εodium citrate). The filterε were baked for 2 hours at 80 β C, prehybridized (50% formamide, 5X SSC, IX Denhardt's solution lmg/mL denatured calf thymus DNA) for 8 hourε at 42°C and hybridized (50% formamide, 5X SSC, IX Denhardt'ε solution lmg/mL denatured calf thymus DNA, 10% dextran sulfate, 1 x 10 6 cpm/mL probe (see the preceeding Example)) overnight. Thereafter, filterε were waεhed twice for 15 minutes with 2X SSC, 0.1% SDS and twice for 15 minutes with 0.5X SSC, 0.1% SDS. Resultε were viεualized by autoradiography. Southern analyεiε of λyPt and yeaεt genomic DNA digeεted with EcoRI and probed with the 0.6 kB fragment revealed that a 0.6 kB piece iε preεent in both digeεtε. Therefore, the 0.6 kB piece iε located in the middle of the cloned DNA. The 0.6 and 1.1 kB EcoRI fragmentε were oriented to each other by εequencing λyPt DNA. The orientation of the 1.7 kB EcoRI fragment waε determined by Southern analysis of yeast genomic DNA digested with PstI and EcoRV, probed with the 0.6 kB EcoRI fragment. A 2.3 kB piece hybridized on thiε blot, locating the EcoRV reεtriction εite in the 1.7 kB fragment towardε the 3' end of the clone. In the other poεsible orientation, with the EcoRV site cloεer to the 5' end, a 1.2 kB fragment would have been releaεed by DNA digested with PstI and EcoRV. SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANT: Donahue, Brian A. Toney, Jeffrey H. Bruhn, Suzanne L. Pil, Pieter H. Brown, Steven Kellett, Patti Essigmann, John M. Lippard, Stephen J. (ii) TITLE OF INVENTION: DNA Structure Specific Recognition Protein and Uses Therefor (iii) NUMBER OF SEQUENCES: 13 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: Hamilton, Brook, Smith & Reynolds, P.C. (B) STREET: 2 Militia Drive (C) CITY: Lexington (D) STATE: MA (E) COUNTRY: USA (F) ZIP: 02173 (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: Floppy disk (B) COMPUTER: IBM PC compatible (C) OPERATING SYSTEM: PC-DOS/MS-DOS (D) SOFTWARE: Patentin Release #1.0, Version /1.25 (vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: US (B ) FILING DATE: (C) CLASSIFICATION: (vii) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: US 07/539,906 (B) FILING DATE: 18-JUN-1990 (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Granahan, Patricia (B) REGISTRATION NUMBER: 32,227 (C) REFERENCE/DOCKET NUMBER: MIT-4787AAA ( ix) TELECOMMUNICATION INFORMATION : (A) TELEPHONE: 617-861-6240 (B) TELEFAX: 617-861-9540 (2) INFORMATION FOR SEQ ID NO:l: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: CC) INDIVIDUAL ISOLATE: Synthetic oligonucleotide (ix) FEATURE: (A) NAME/KEY: miβc difference (B) LOCATION: replace(11..12) (D) OTHER INFORMATION: /label- Pt-DNA /note* "ciβ-{Pt(NH3)3} l,2-d(GpG) intrastrand Platinated DNA Structural Motif" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:l: TCTCCTTCTT GGTTCTCTTC TC 22 (2) INFORMATION FOR SEQ ID NO:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Synthetic oligonucleotide (ix) FEATURE: (A) NAME/KEY: misc difference (B) LOCATION: replace(11..12) (D) OTHER INFORMATION: /label= Pt-DNA /note= "cis-{Pt(NH3)2} l,2-d(ApG) intrastrand Platinated DNA Structural Motif" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: TCTCCTTCTT AGTTCTCTTC TC 22 (2) INFORMATION FOR SEQ ID NO:3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Synthetic oligonucleotide (ix) FEATURE: (A) NAME/KEY: misc_difference (B) LOCATION: replace(11..13) (D) OTHER INFORMATION: /label= Pt-DNA /note= "ciB-{Pt(NH3)2} l,3-d(GpTρG) intrastrand Platinated DNA Structural Motif" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: TCTCCTTCTT GTGTCTCTTC TC 22 (2) INFORMATION FOR SEQ ID NO: : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Synthetic oligonucleotide (ix) FEATURE: (A) NAME/KEY: iβc difference (B) LOCATION: replace(11..13) (D) OTHER INFORMATION: /label= Pt-DNA /note= "trans-{Pt(NH3)2> l,3-d(GpTpG) intrastrand Platinated DNA Structural Motif" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: TCTCCTTCTT GTGTCTCTTC TC 22 (2) INFORMATION FOR SEQ ID NO:5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (C) INDIVIDUAL ISOLATE: Synthetic oligonucleotide (ix) FEATURE: (A) NAME/KEY: misc_difference (B) LOCATION: replace(12) (D) OTHER INFORMATION: /label= Pt-DNA /note= "ciβ-{Pt(NH3)2(N3-cytosine)} dG monofunctional Platinated DNA Structural Motif" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: TCTCCTTCTT CGTTCTCTTC TC 22 (2) INFORMATION FOR SEQ ID NO:6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2839 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (vii) IMMEDIATE SOURCE: (B) CLONE: human SSRP - composite of six overlapping cDNA clones (viii) POSITION IN GENOME: (A) CHROMOSOME/SEGMENT: llql2 (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 275..2404 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: GAATTCCGTA CGGCTTCCGG TGGCGGGACG CGGGGCCGCG CACGCGGGAA AAGCTTCCCC 60 GGTGTCCCCC CATCCCCCTC CCCGCGCCCC CCCCGCGTCC CCCCAGCGCG CCCACCTCTC 120 GCGCCGGGGC CCTCGCGAGG CCGCAGCCTG AGGAGATTCC CAACCTGCTG AGCATCCGCA 180 CACCCACTCA GGAGTTGGGG CCCAGCTCCC AGTTTACTTG GTTTCCCTTG TGCAGCCTGG 240 GGCTCTGCCC AGGCCACCAC AGGCAGGGGT CGAC ATG GCA GAG ACA CTG GAG 292 Met Ala Glu Thr Leu Glu 1 5 TTC AAC GAC GTC TAT CAG GAG GTG AAA GGT TCC ATG AAT GAT GGT CGA 340 Phe Asn Asp Val Tyr Gin Glu Val Lye Gly Ser Met Aβn Asp Gly Arg 10 15 20 CTG AGG TTG AGC CGT CAG GGC ATC ATC TTC AAG AAT AGC AAG ACA GGC 388 Leu Arg Leu Ser Arg Gin Gly lie lie Phe Lys Aβn Ser Lys Thr Gly 25 30 35 AAA GTG GAC AAC ATC CAG GCT GGG GAG TTA ACA GAA GGT ATC TGG CGC 436 Lys Val Asp Asn lie Gin Ala Gly Glu Leu Thr Glu Gly lie Trp Arg 40 45 50 CGT GTT GCT CTG GGC CAT GGA CTT AAA CTG CTT ACA AAG AAT GGC CAT 484 Arg Val Ala Leu Gly His Gly Leu Lys Leu Leu Thr Lys Asn Gly His 55 60 65 70 GTC TAC AAG TAT GAT GGC TTC CGA GAA TCG GAG TTT GAG AAA CTC TCT 532 Val Tyr Lye Tyr Asp Gly Phe Arg Glu Ser Glu Phe Glu Lys Leu Ser 75 80 85 GAT TTC TTC AAA ACT CAC TAT CGC CTT GAG CTA ATG GAG AAG GAC CTT 580 Asp Phe Phe Lys Thr His Tyr Arg Leu Glu Leu Met Glu Lys Asp Leu 90 95 100 TGT GTG AAG GGC TGG AAC TGG GGG ACA GTG AAA TTT GGT GGG CAG CTG 628 Cys Val Lys Gly Trp Asn Trp Gly Thr Val Lys Phe Gly Gly Gin Leu 105 110 115 CTT TCC TTT GAC ATT GGT GAC CAG CCA GTC TTT GAG ATA CCC CTC AGC 676 Leu Ser Phe Asp lie Gly Asp Gin Pro Val Phe Glu lie Pro Leu Ser 120 125 130 AAT GTG TCC CAG TGC ACC ACA GGC AAG AAT GAG GTG ACA CTG GAA TTC 724 Asn Val Ser Gin Cys Thr Thr Gly Lys Asn Glu Val Thr Leu Glu Phe 135 140 145 150 CAC CAA AAC GAT GAC GCA GAG GTG TCT CTC ATG GAG GTG CGC TTC TAC 772 His Gin Asn Asp Asp Ala Glu Val Ser Leu Met Glu Val Arg Phe Tyr 155 160 165 GTC CCA CCC ACC CAG GAC GAT GGT GTG GAC CCT GTT GAG GCC TTT GCC 820 Val Pro Pro Thr Gin Glu Asp Gly Val Asp Pro Val Glu Ala Phe Ala 170 175 180 CAG AAT GTG TTG TCA AAG GCG GAT GTA ATC CAG GCC ACG GGA GAT GCC 868 Gin Asn Val Leu Ser Lys Ala Asp Val lie Gin Ala Thr Gly Asp Ala 185 190 195 ATC TGC ATC TTC CGG GAG CTG CAG TGT CTG ACT CCT CGT GGT CGT TAT 916 lie Cys lie Phe Arg Glu Leu Gin Cys Leu Thr Pro Arg Gly Arg Tyr 200 205 210 GAC ATT CGG ATC TAC CCC ACC TTT CTG CAC CTG CAT GGC AAG ACC TTT 964 Asp He Arg He Tyr Pro Thr Phe Leu His Leu His Gly Lys Thr Phe 215 220 225 230 GAC TAC AAG ATC CCC TAC ACC ACA GTA CTG CGT CTG TTT TTG TTA CCC 1012 Asp Tyr Lys He Pro Tyr Thr Thr Val Leu Arg Leu Phe Leu Leu Pro 235 240 245 CAC AAG GAC CAG CGC CAG ATG TTC TTT GTG ATC AGC CTG GAT CCC CCA 1060 His Lye Asp Gin Arg Gin Met Phe Phe Val He Ser Leu Asp Pro Pro 250 255 260 ATC AAG CAA GGC CAA ACT CGC TAC CAC TTC CTG ATC CTC CTC TTC TCC 1108 He Lys Gin Gly Gin Thr Arg Tyr His Phe Leu He Leu Leu Phe Ser 265 270 275 AAG GAC GAG GAC ATT TCG TTG ACT CTG AAC ATG AAC GAG GAA GAA GTG 1156 Lys Asp Glu Asp He Ser Leu Thr Leu Asn Met Aβn Glu Glu Glu Val 280 285 290 GAG AAG CGC TTT GAG GGT CGG CTC ACC AAG AAC ATG TCA GGA TCC CTC 1204 Glu Lys Arg Phe Glu Gly Arg Leu Thr Lys Asn Met Ser Gly Ser Leu 295 300 305 310 TAT GAG ATG GTC AGC CGG GTC ATG AAA GCA CTG GTA AAC CGC AAG ATC 1252 Tyr Glu Met Val Ser Arg Val Met Lys Ala Leu Val Asn Arg Lys He 315 320 325 ACA GTG CCA GGC AAC TTC CAA GGG CAC TCA GGG GCC CAG TGC ATT ACC 1300 Thr Val Pro Gly Asn Phe Gin Gly His Ser Gly Ala Gin Cyβ He Thr 330 335 340 TGT TCC TAC AAG GCA AGC TCA GGA CTG CTC TAC CCG CTG GAG CGG GGC 1348 Cys Ser Tyr Lys Ala Ser Ser Gly Leu Leu Tyr Pro Leu Glu Arg Gly 345 350 355 TTC ATC TAC GTC CAC AAG CCA CCT GTG CAC ATC CGC TTC GAT GAG ATC 1396 Phe He Tyr Val His Lye Pro Pro Val His He Arg Phe Aβp Glu He 360 365 370 TCC TTT GTC AAC TTT GCT CGT GGT ACC ACT ACT ACT CGT TCC TTT GAC 1444 Ser Phe Val Asn Phe Ala Arg Gly Thr Thr Thr Thr Arg Ser Phe Asp 375 380 385 390 TTT GAA ATT GAG ACC AAG CAG GGC ACT CAG TAT ACC TTC AGC AGC ATT 1492 Phe Glu He Glu Thr Lye Gin Gly Thr Gin Tyr Thr Phe Ser Ser He 395 400 405 GAG AGG GAG GAG TAC GGG AAA CTG TTT GAT TTT GTC AAC GCG AAA AAG 1540 Glu Arg Glu Glu Tyr Gly Lys Leu Phe Asp Phe Val Asn Ala Lys Lys 410 415 420 CTC AAC ATC AAA AAC CGA GGA TTG AAA. GAG GGC ATG AAC CCA AGC TAC 1588 Leu Asn He Lys Asn Arg Gly Leu Lys Glu Gly Met λβn Pro Ser Tyr 425 430 435 GAT GAA TAT GCT GAC TCT GAT GAG GAC CAG CAT GAT GCC TAC TTG GAG 1636 λβp Glu Tyr Ala Asp Ser Asp Glu Asp Gin His Asp Ala Tyr Leu Glu 440 445 450 AGG ATG AAG GAG GAA GGC AAG ATC CGG GAG GAG AAT GCC AAT GAC AGC 1684 Arg Met Lys Glu Glu Gly Lys He Arg Glu Glu Asn Ala Asn Asp Ser 455 460 465 470 AGC GAT GAC TCA GGA GAA GAA ACC GAT GAG TCA TTC AAC CCA GGT GAA 1732 Ser Aβp Asp Ser Gly Glu Glu Thr Asp Glu Ser Phe Aβn Pro Gly Glu 475 480 485 GAG GAG GAA GAT GTG GCA GAG GAG TTT GAC AGC AAC GCC TCT GCC AGC 1780 Glu Glu Glu Aβp Val Ala Glu Glu Phe Asp Ser Asn Ala Ser Ala Ser 490 495 500 TCC TCC AGT AAT GAG GGT GAC AGT GAC CGG GAT GAG AAG AAG CGG AAA 1828 Ser Ser Ser Aβn Glu Gly Asp Ser Asp Arg Aβp Glu Lye Lys Arg Lys 505 510 515 CAG CTC AAA AAG GCC AAG ATG GCC AAG GAC CGC AAG AGC CGC AAG AAG 1876 Gin Leu Lys Lys Ala Lys Met Ala Lys Asp Arg Lys Ser Arg Lys Lye 520 525 530 CCT GTG GAG GTG AAG AAG GGC AAA GAC CCC AAT GCC CCC AAG AGG CCC 1924 Pro Val Glu Val Lys Lys Gly Lys Asp Pro Asn Ala Pro Lys Arg Pro 535 540 545 550 ATG TCT GCA TAC ATG CTG TGG CTC AAT GCC AGC CGA GAG AAG ATC AAG 1972 Met Ser Ala Tyr Met Leu Trp Leu Asn Ala Ser Arg Glu Lys He Lye 555 560 565 TCA GAC CAT CCT GGC ATC AGC ATC ACG GAT CTT TCC AAG AAG GCA GGC 2020 Ser Asp His Pro Gly He Ser He Thr Asp Leu Ser Lys Lye Ala Gly 570 575 580 GAG ATC TGG AAG GGA ATG TCC AAA GAG AAG AAA GAG GAG TGG GAT CGC 2068 Glu He Trp Lys Gly Met Ser Lye Glu Lye Lys Glu Glu Trp Aβp Arg 585 590 595 AAG GCT GAG GAT GCC AGG AGG GAC TAT GAA AAA GCC ATG AAA GAA TAT 2116 Lys Ala Glu Aβp Ala Arg Arg Asp Tyr Glu Lys Ala Met Lye Glu Tyr 600 605 610 GAA GGG GGC CGA GGC GAG TCT TCT AAG AGG GAC AAG TCA AAG AAG AAG 2164 Glu Gly Gly Arg Gly Glu Ser Ser Lys Arg Asp Lys Ser Lys Lye Lye 615 620 625 630 AAG AAA GTA AAG GTA AAG ATG GAA AAG AAA TCC ACG CCC TCT AGG GGC 2212 Lys Lys Val Lys Val Lys Met Glu Lys Lys Ser Thr Pro Ser Arg Gly 635 640 645 TCA TCA TCC AAG TCG TCC TCA AGG CAG CTA AGC GAG AGC TTC AAG AGC 2260 Ser Ser Ser Lys Ser Ser Ser Arg Gin Leu Ser Glu Ser Phe Lys Ser 650 655 660 AAA GAG TTT GTG TCT AGT GAT GAG AGC TCT TCG GGA GAG AAC AAG AGC 2308 Lys Glu Phe Val Ser Ser Asp Glu Ser Ser Ser Gly Glu Asn Lys Ser 665 670 675 AAA AAG AAG AGG AGG AGG AGC GAG GAC TCT GAA GAA GAA GAA CTA GCC 2356 Lys Lys Lys Arg Arg Arg Ser Glu Asp Ser Glu Glu Glu Glu Leu Ala 680 685 690 AGT ACT CCC CCC AGC TCA GAG GAC TCA GCG TCA GGA TCC GAT GAG TAGAAACGGA 2411 Ser Thr Pro Pro Ser Ser Glu Asp Ser Ala Ser Gly Ser Asp Glu 695 700 705 710 GGAAGGTTCT CTTTGCGCTT GCCTTCTCAC ACCCCCCGAC TCCCCACCCA TATTTTGGTA 2471 CCAGTTTCTC CTCATGAAAT GCAGTCCCTG GATTCTGTGC CATCTGAACA TGCTCTCCTG 2531 TTGGTGTGTA TGTCACTAGG GCAGTGGGGA GACGTCTTAA CTCTGCTGCT TCCCAAGGAT 2591 GGCTGTTTAT AATTTGGGGA GAGATAGGGT GGGAGGCAGG GCAATGCAGG ATCCAAATCC 2651 TCATCTTACT TTCCCGACCT TAAGGATGTA GCTGCTGCTT GTCCTGTTCA AGTTGCTGGA 2711 GCAGGGGTCA TGTGAGGCCA GGCCTGTAGC TCCTACCTGG GGCCTATTTC TACTTTCATT 2771 TTGTATTTCT GGTCTGTGAA AATGATTTAA TAAAGGGAAC TGACTTTGGA AACCAAAAAA 2831 AGGAATTC 2839 (2) INFORMATION FOR SEQ ID NO:7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 709 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (vii) IMMEDIATE SOURCE: (B) CLONE: human SSRP (predicted) (ix) FEATURE: (A) NAME/KEY: Domain (B) LOCATION: 440..496 (D) OTHER INFORMATION: /label= Acidic (ix) FEATURE: (A) NAME /KEY: Domain (B ) LOCATION : 512 . . 534 (D) OTHER INFORMATION: /label= Basic I (ix) FEATURE: (A) NAME/KEY: Domain (B) LOCATION: 539..614 (D) OTHER INFORMATION: /label- HMG-box (ix) FEATURE: (A) NAME/KEY: Domain (B) LOCATION: 623..640 (D) OTHER INFORMATION: /label- Basic II (ix) FEATURE: (A) NAME/KEY: Domain (B) LOCATION: 661..709 (D) OTHER INFORMATION: /label- Mixed Charge (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: Het Ala Glu Thr Leu Glu Phe Asn Asp Val Tyr Gin Glu Val Lye Gly 1 5 10 15 Ser Met Aβn Asp Gly Arg Leu Arg Leu Ser Arg Gin Gly He He Phe 20 25 30 Lys Aβn Ser Lys Thr Gly Lys Val Asp Asn He Gin Ala Gly Glu Leu 35 40 45 Thr Glu Gly He Trp Arg Arg Val Ala Leu Gly His Gly Leu Lye Leu 50 55 60 Leu Thr Lye Aβn Gly Hie Val Tyr Lys Tyr Aβp Gly Phe Arg Glu Ser 65 70 75 80 Glu Phe Glu Lys Leu Ser Aβp Phe Phe Lye Thr Hie Tyr Arg Leu Glu 85 90 95 Leu Met Glu Lys Aβp Leu Cyβ Val Lye Gly Trp Aβn Trp Gly Thr Val 100 105 110 Lye Phe Gly Gly Gin Leu Leu Ser Phe Asp He Gly Asp Gin Pro Val 115 120 125 Phe Glu He Pro Leu Ser Asn Val Ser Gin Cys Thr Thr Gly Lye Aβn 130 135 140 Glu Val Thr Leu Glu Phe His Gin Aεn Aβp Aβp Ala Glu Val Ser Leu 145 150 155 160 Met Glu Val Arg Phe Tyr Val Pro Pro Thr Gin Glu Aβp Gly Val Aβp 165 170 175 Pro Val Glu Ala Phe Ala Gin Aβn Val Leu Ser Lys Ala Aβp Val He 180 185 190 Gin Ala Thr Gly Asp Ala He Cys He Phe Arg Glu Leu Gin Cys Leu 195 200 205 Thr Pro Arg Gly Arg Tyr Asp He Arg He Tyr Pro Thr Phe Leu Hie 210 215 220 Leu His Gly Lys Thr Phe Aep Tyr Lys He Pro Tyr Thr Thr Val Leu 225 230 235 240 λrg Leu Phe Leu Leu Pro His Lys λβp Gin Arg Gin Met Phe Phe Val 245 250 255 He Ser Leu Aβp Pro Pro He Lys Gin Gly Gin Thr Arg Tyr His Phe 260 265 270 Leu He Leu Leu Phe Ser Lys Asp Glu Asp He Ser Leu Thr Leu Aβn 275 280 285 Met Asn Glu Glu Glu Val Glu Lys Arg Phe Glu Gly Arg Leu Thr Lys 290 295 300 Asn Met Ser Gly Ser Leu Tyr Glu Met Val Ser Arg Val Met Lys Ala 305 310 315 320 Leu Val Asn Arg Lys He Thr Val Pro Gly Aβn Phe Gin Gly Hie Ser 325 330 335 Gly Ala Gin Cyβ He Thr Cyβ Ser Tyr Lye Ala Ser Ser Gly Leu Leu 340 345 350 Tyr Pro Leu Glu Arg Gly Phe He Tyr Val Hie Lys Pro Pro Val His 355 360 365 He Arg Phe Asp Glu He Ser Phe Val Asn Phe Ala Arg Gly Thr Thr 370 375 380 Thr Thr Arg Ser Phe Asp Phe Glu He Glu Thr Lys Gin Gly Thr Gin 385 390 395 400 Tyr Thr Phe Ser Ser He Glu Arg Glu Glu Tyr Gly Lys Leu Phe Aβp 405 410 415 Phe Val Aβn Ala Lys Lys Leu Aβn He Lye Asn Arg Gly Leu Lys Glu 420 425 430 Gly Met Asn Pro Ser Tyr Asp Glu Tyr Ala Aβp Ser Asp Glu Asp Gin 435 440 445 His Asp Ala Tyr Leu Glu Arg Met Lys Glu Glu Gly Lys He Arg Glu 450 455 460 Glu Asn Ala Aεn Asp Ser Ser Asp Asp Ser Gly Glu Glu Thr Asp Glu 465 470 475 480 Ser Phe Aβn Pro Gly Glu Glu Glu Glu Asp Val Ala Glu Glu Phe Asp 485 490 495 Ser Aβn Ala Ser Ala Ser Ser Ser Ser Aβn Glu Gly Asp Ser Aβp Arg 500 505 510 Aβp Glu Lye Lys Arg Lys Gin Leu Lys Lys Ala Lys Met Ala Lys Aβp 515 520 525 Arg Lye Ser Arg Lys Lys Pro Val Glu Val Lys Lys Gly Lys Aβp Pro 530 535 540 Aβn Ala Pro Lys Arg Pro Met Ser Ala Tyr Met Leu Trp Leu Asn Ala 545 550 555 560 Ser Arg Glu Lys He Lys Ser Asp His Pro Gly He Ser He Thr Asp 565 570 575 Leu Ser Lys Lye Ala Gly Glu He Trp Lys Gly Met Ser Lys Glu Lys 580 585 590 Lys Glu Glu Trp Asp λrg Lys Ala Glu Asp Ala λrg λrg λβp Tyr Glu 595 600 605 Lye λla Met Lys Glu Tyr Glu Gly Gly λrg Gly Glu Ser Ser Lys λrg 610 615 620 Asp Lye Ser Lys Lys Lys Lye Lys Val Lys-Val Lys Met Glu Lye Lys 625 630 635 640 Ser Thr Pro Ser λrg Gly Ser Ser Ser Lye Ser Ser Ser λrg Gin Leu 645 650 655 Ser Glu Ser Phe Lys Ser Lye Glu Phe Val Ser Ser λβp Glu Ser Ser 660 665 670 Ser Gly Glu Asn Lye Ser Lyε Lys Lye Arg Arg Arg Ser Glu Aβp Ser 675 680 685 Glu Glu Glu Glu Leu Ala Ser Thr Pro Pro Ser Ser Glu Aβp Ser Ala 690 695 700 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1898 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (vii) IMMEDIATE SOURCE: (A) LIBRARY: Human B cell (B) CLONE: lambda-Ptl (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: GAATTCCACC AAAACGATGA CGCAGAGGTG TCTCTCATGG AGGTGCGCTT CTACGTCCCA 60 CCCACCCAGG AGGATGGTGT GGACCCTGTT GAGGCCTTTG CCCAGAATGT GTTGTCAAAG 120 GCGGATGTAA TCCAGGCCAC GGGAGATGCC ATCTGCATCT TCCGGGAGCT GCAGTGTCTG 180 ACTCCTCGTG GTCGTTATGA CATTCGGATC TACCCCACCT TTCTGCACCT GCATGGCAAG 240 ACCTTTGACT ACAAGATCCC CTACACCACA GTACTGCGTC TGTTTTTGTT ACCCCACAAG 300 GACCAGCGCC AGATGTTCTT TGTGATCAGC CTGGATCCCC CAATCAAGCA AGGCCAAACT 360 CGCTACCACT TCCTGATCCT CCTCTTCTCC AAGGACGAGG ACATTTCGTT GACTCTGAAC 420 ATGAACGAGG AAGAAGTGGA GAAGCGCTTT GAGGGTCGGC TCACCAAGAA CATGTCAGGA 480 TCCCTCTλTG AGλTGGTCλG CCGGGTCATG AλAGCACTGG TλAACCGCλλ GATCACAGTG 540 CCAGGCλλCT TCCλλGGGCA CTCλGGGGCC CAGTGCλTTA CCTGTTCCTA CAAGGCλλGC 600 TCλGGACTGC TCTACCCGCT GGAGCGGGGC TTCATCTλCG TCCλCλλGCC λCCTGTGCλC 660 ATCCGCTTCG ATGλGλTCTC CTTTGTCλλC TTTGCTCGTG GTλCCλCTλC TλCTCGTTCC 720 TTTGλCTTTG AλλTTGλGλC CλλGCλGGGC λCTCAGTATA CCTTCλGCAG CATTGλGλGG 780 GAGGAGTACG GGAAACTGTT TGλTTTTGTC λλCGCGλλλλ λGCTCλλCλT CAAAAACCGA 840 GGATTGAλλG AGGGCATGAA CCCλAGCTAC GATGAATATG CTGACTCTGλ TGAGGACCAG 900 CATGATGCCT ACTTGGAGAG GATGAAGGAG GAAGGCAAGA TCCGGGAGGA GλλTGCCλAT 960 GACAGCAGCG λTGACTCAGG AGAAGAAACC GλTGλGTCAT TCAACCCAGG TGAAGAGGAG 1020 GAAGλTGTGG CAGAGGAGTT TGACAGCAAC GCCTCTGCCA GCTCCTCCAG TAATGAGGGT 1080 GACAGTGACC GGGATGAGAA GAAGCGGAAA CAGCTCAAAA AGGCCAAGAT GGCCAAGGAC 1140 CGCAAGAGCC GCAAGAAGCC TGTGGAGGTG AAGAAGGGCA AAGACCCCAA TGCCCCCAλG 1200 λGGCCCλTGT CTGCATACAT GCTGTGGCTC AλTGCCλGCC GAGAGAAGAT CAAGTCAGAC 1260 CATCCTGGCA TCAGCATCAC GGATCTTTCC AλGAAGGCAG GCGAGATCTG GAAGGGAλTG 1320 TCCAAAGAGA AGλAAGAGGA GTGGGATCGC AAGGCTGAGG ATGCCAGGAG GGACTATGAA 1380 AAAGCCATGA AAGAATATGA AGGGGGCCGA GGCGAGTCTT CTAAGAGGGA CAAGTCAλλG 1440 AAGAAGAAGA AAGTAAAGGT AAAGATGGAA AAGλAATCCA CGCCCTCTAG GGGCTCλTCA 1500 TCCAAGTCGT CCTCAAGGCA GCTAAGCGAG λGCTTCAAGA GCAAAGAGTT TGTGTCTAGT 1560 GATGAGAGCT CTTCGGGAGA GAACAAGAGC AAAAAGAAGA GGAGGAGGAG CGAGGACTCT 1620 GAAGAAGAAG AACTAGCCAG TACTCCCCCC AGCTCAGAGG ACTCAGCGTC AGGATCCGAT 1680 GAGTAGAAAC GGAGGAAGGT TCTCTTTGCG CTTGCCTTCT CACACCCCCC GACTCCCCAC 1740 CCATATTTTG GTACCAGTTT CTCCTCATGA AATGCAGTCC CTGGATTCTG TGCCATCTGA 1800 ACATGCTCTC CTGTTGGTGT GTATGTCACT AGGGCAGTGG GGAGACGTCT TAACTCTGCT 1860 GCTTCCCAAG GATGGCTGTT TATAATTTGG GGAGAGAT 1898 (2 ) INFORMATION FOR SEQ ID NO : 9 : ( i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 1444 base pairs ( B ) TYPE : nucleic acid (C ) STRANDEDNESS : double (D ) TOPOLOGY : linear (ii) MOLECULE TYPE: cDNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (vii) IMMEDIATE SOURCE: (λ) LIBRARY: Human B cell (B ) CLONE : lambda Pt2 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9 : GAATTCCACC AλλλCGλTGλ CGCλGλGGTG TCTCTCλTGG λGGTGCGCTT CTλCGTCCCλ 60 CCCλCCCλGG λGGλTGGTGT GGλCCCTGTT GλGGCCTTTG CCCλGλλTGT GTTGTCλλλG 120 GCGGλTGTλλ TCCλGGCCλC GGGλGλTGCC ATCTGCλTCT TCCGGGAGCT GCAGTGTCTG 180 ACTCCTCGTG GTCGTTATGλ CλTTCGGλTC TλCCCCλCCT TTCTGCλCCT GCλTGGCλλG 240 ACCTTTGλCT λCλλGλTCCC CTλCACCλCλ GTACTGCGTC TGTTTTTGTT ACCCCλCλλG 300 GλCCAGCGCC λGλTGTTCTT TGTGATCAGC CTGGATCCCC CAλTCAAGCA λGGCCAAACT 360 CGCTACCACT TCCTGATCCT CCTCTTCTCC AAGGACGAGG ACATTTCGTT GACTCTGAAC 420 ATGAACGAGG AAGAAGTGGA GAAGCGCTTT GAGGGTCGGC TCACCAAGAA CATGTCAGGA 480 TCCCTCTATG AGATGGTCAG CCGGGTCATG AAAGCACTGG TAAACCGCAA GATCACAGTG 540 CCAGGCAACT TCCAAGGGCA CTCAGGGGCC CAGTGCATTA CCTGTTCCTA CλAGGCAAGC 600 TCλGGACTGC TCTλCCCGCT GGAGCGGGGC TTCλTCTACG TCCACAλGCC λCCTGTGCAC 660 ATCCGCTTCG ATGλGATCTC CTTTGTCAAC TTTGCTCGTG GTACCACTAC TACTCGTTCC 720 TTTGACTTTG AAATTGAGAC CAAGCAGGGC ACTCλGTATA CCTTCAGCAG CATTGAGAGG 780 GAGGAGTACG GGAλACTGTT TGATTTTGTC AACGCGAAAA AGCTCAACAT CAAAAACCGA 840 GGATTGAAAG AGGGCATGAA CCCAAGCTAC GATGAATATG CTGACTCTGA TGAGGACCAG 900 CλTGATGCCT ACTTGGAGAG GATGAAGGAG GAAGGCAAGA TCCGGGAGGA GAATGCCAAT 960 CACAGCAGCG ATGACTCAGG AGAAGAAACC GATGAGTCAT TCAACCCAGG TGAAGAGGAG 1020 GAAGATGTGG CAGAGGAGTT TGACAGCAAC GCCTCTGCCA GCTCCTCCAG TAATGAGGGT 1080 GACAGTGACC GGGATGAGAA GAAGCGGAAA CAGCTCAAAA AGGCCAAGAT GGCCAAGGAC 1140 CGCAAGAGCC GCAAGAAGCC TGTGGAGGTG AAGAAGGGCA AAGACCCCAA TGCCCCCAAG 1200 AGGCCCATGT CTGCATACAT GCTGTGGCTC AATGCCAGCC GAGAGAAGAT CAAGTCAGAC 1260 CATCCTGGCλ TCAGCATCAC GGATCTTTCC AAGAAGGCAG GCGAGATCTG GAAGGGAATG 1320 TCCAAAGAGA AGAAAGAGGA GTGGGATCGC AAGGCTGAGG ATGCCAGGAG GGACTATGAA 1380 AAAGCCATGA AAGAATATGA AGGGGGCCGA GGCGAGTCTT CTAAGAGGGA CAAGTCAAAG 1440 AAGA 1444 (2) INFORMATION FOR SEQ ID NO: 10 : (i) SEQUENCE CHARACTERISTICS : (A) LENGTH: 2384 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS : double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (vi) ORIGINAL SOURCE: (λ) ORGANISM: Drosophila melanogaster (vii) IMMEDIATE SOURCE: (B) CLONE: Drosophila SSRP - composite sequence (viii) POSITION IN GENOME: (A) CHROMOSOME/SEGMENT: 2 (B) MAP POSITION: 60A 1-4 (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 123..2291 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: GAATTCCGCG CGCAGTGTTG TTTTGTGTCT GCCGGAATTA TTGTAAATTG GTGACAATTT 60 CGCAAGGCGG CGTAATACAT AGTTGATCTA TTATCTTGTT ACTGGAGAGG AAGAAGTGCA 120 GG ATG λCA GAC TCT CTG GAG TAC AAC GAC ATA AAC GCC GAA GTG CGC 167 Met Thr Aβp Ser Leu Glu Tyr Aβn Aβp He Aβn Ala Glu Val Arg 1 5 10 15 GGA GTC TTG TGT TCC GGA CGC CTA AAG ATG ACC GAG CAG AAC ATC ATC 215 Gly Val Leu Cys Ser Gly Arg Leu Lys Met Thr Glu Gin Aβn He He 20 25 30 TTC AAG AAC λCC AAG ACC GGC AAG GTG GAG CAG ATC TCG GCA GAG GAC 263 Phe Lye Asn Thr Lys Thr Gly Lys Val Glu Gin He Ser Ala Glu Asp 35 40 45 ATA GAC CTG ATC AAT TCG CAG AAG TTC GTG GGC ACC TGG GGA CTG AGG 311 He Aβp Leu He Asn Ser Gin Lys Phe Val Gly Thr Trp Gly Leu Arg 50 55 60 GTG TTC ACC AAA GGC GGC GTG CTC CAC CGC TTC ACC GGA TTC CGC GAC 359 Val Phe Thr Lye Gly Gly Val Leu Hie Arg Phe Thr Gly Phe Arg Asp 65 70 75 AGC GAG CAC GAG AAG CTG GGC AAG TTT ATC AAG GCT GCC TAC TCG CAG 407 Ser Glu His Glu Lys Leu Gly Lys Phe He Lye Ala Ala Tyr Ser Gin 80 85 90 95 GAG ATG " GTC GAG AAG GAG ATG TGC GTC AAG GGC TGG AAC TGG GGC ACC 455 Glu Met Val Glu Lys Glu Met Cys Val Lye Gly Trp Asn Trp Gly Thr 100 105 110 GCC CGC TTC ATG GGC TCC GTC CTG AGC TTC GAC AAG GAG TCG AAG ACC 503 Ala λrg Phe Met Gly Ser Val Leu Ser Phe Asp Lys Glu Ser Lys Thr 115 120 125 ATC TTC GAG GTG CCG CTG TCG CAC GTT TCG CAG TGC GTG ACC GGC AAG 551 He Phe Glu Val Pro Leu Ser His Val Ser Gin Cys Val Thr Gly Lys 130 135 140 AAC GAG GTC ACC CTG GAG TTC CAC CAA AAC GAC GAT GCG CCC GTG GGT 599 λsn Glu Val Thr Leu Glu Phe Hie Gin λsn Aβp Aβp Ala Pro Val Gly 145 150 155 CTA CTG GAG ATG CGG TTC CAC ATA CCC GCC GTG GAG TCG GCC GAG GAG 647 Leu Leu Glu Met λrg Phe His He Pro λla Val Glu Ser λla Glu Glu 160 165 170 175 GAT CCG GTλ GλC λλG TTC CλC CλG AAC GTλ λTG λGC AAG GCC TCG GTC 695 Asp Pro Val Asp Lye Phe His Gin Asn Val Met Ser Lys λla Ser Val 180 185 190 ATC TCG GCT TCG GGC GAG TCC ATC GCC ATT TTC AGA GAG ATC CAG λTC 7 3 He Ser λla Ser Gly Glu Ser He λla He Phe λrg Glu He Gin He 195 200 205 CTC λCG CCT CGC GGT CGC TAT GAC ATC AλG λTC TTC TCG λCC TTC TTC 791 Leu Thr Pro λrg Gly Arg Tyr Aβp He Lys He Phe Ser Thr Phe Phe 210 215 220 CAG CTG CAC GGC AAG ACG TTC GAC TAC AAG ATT CCC ATG GAC TCG GTG 839 Gin Leu Hie Gly Lye Thr Phe Aβp Tyr Lys He Pro Met Asp Ser Val 225 230 235 CTG CGG CTC TTC ATG CTG CCC CAC AAA GAC AGT CGA CAG ATG TTC TTT 887 Leu Arg Leu Phe Met Leu Pro His Lys Asp Ser Arg Gin Met Phe Phe 240 245 250 255 GTG CTC TCC TTG GAT CCG CCC ATC AAG CAG GGA CAA ACG CGT TAC CAC 935 Val Leu Ser Leu Asp Pro Pro He Lys Gin Gly Gin Thr Arg Tyr Hie 260 265 270 TAC CTG GTC CTG CTG TTT GCT CCC GAT GAG GAG ACC ACC ATT GAG CTG 983 Tyr Leu Val Leu Leu Phe Ala Pro Aβp Glu Glu Thr Thr He Glu Leu 275 280 285 CCA TTC TCG GAA GCC GAG TTG CGA GAC AAG TAC GAG GGC AAG CTG GAG 1031 Pro Phe Ser Glu Ala Glu Leu Arg Aβp Lys Tyr Glu Gly Lye Leu Glu 290 295 300 AAA GAG ATC TCC GGG CCG GTG TAC GAG GTG ATG GGC AAA GTG ATG AAG 1079 Lys Glu He Ser Gly Pro Val Tyr Glu Val Met Gly Lys Val Met Lys 305 310 315 GTG CTG ATC GGT CGA AAA ATT ACC GGA CCC GGT AAC TTT ATC GGA CAC 1127 Val Leu He Gly Arg Lys He Thr Gly Pro Gly Asn Phe He Gly His 320 325 330 335 TCT GGC ACG GCT GCA GTG GGC TGC TCG TTC AAG GCT GCA GCT GGA TAT 1175 Ser Gly Thr Ala Ala Val Gly Cys Ser Phe Lys Ala Ala Ala Gly Tyr 340 345 350 CTG TAT CCC CTG GAG CGA GGA TTC ATC TAT ATC CAC AAG CCA CCG CTG 1223 Leu Tyr Pro Leu Glu Arg Gly Phe He Tyr He Hie Lys Pro Pro Leu 355 360 365 CAT ATC CGC TTT GAG GAG ATT AGT TCT GTG AAC TTT GCC CGC AGC GGC 1271 His He Arg Phe Glu Glu He Ser Ser Val Asn Phe Ala Arg Ser Gly 370 375 380 GGA TCC ACG CGA TCT TTC GAC TTC GAA GTG ACG CTC AAG AAC GGA ACT 1319 Gly Ser Thr Arg Ser Phe Asp Phe Glu Val Thr Leu Lys Asn Gly Thr 385 390 395 GTT CAC ATC TTC TCC TCC ATC GAG AλG GAG GAG TAT GCC λλG CTC TTC 1367 Val His He Phe Ser Ser He Glu Lys Glu Glu Tyr λla Lys Leu Phe 400 405 410 415 GAC TAC ATC ACA CAG λλG AAG TTG CAT GTC AGC AAC ATG GGC λλG GλC 1415 λsp Tyr He Thr Gin Lys Lys Leu His Val Ser λsn Met Gly Lys Asp 420 425 430 AAG AGC GGC TAC λλG GλC GTG GλC TTT GGT GλT TCG GλC AAC GλG AAC 1463 Lys Ser Gly Tyr Lye Asp Val λsp Phe Gly λsp Ser λsp λsn Glu λβn 435 440 445 GAA CCA GAT GCC TAT CTG GCT CGC CTC AAG GCT GAG GCG λGG GAA λλG 1511 Glu Pro λsp λla Tyr Leu λla λrg Leu Lys λla Glu λla λrg Glu Lye 450 455 460 GAG GAG GAC GAC GAC GAT GGC GAC TCG GAT GAA GAG TCC ACG GAT GλG 1559 Glu Glu Asp λsp λsp λβp Gly Aβp Ser Asp Glu Glu Ser Thr λsp Glu 465 470 475 GAC TTC AAG CCC AAC GAG AAC GAG TCC GAT GTG GCC GAG GAG TAT GAC 1607 Asp Phe Lys Pro Aβn Glu Asn Glu Ser Aβp Val Ala Glu Glu Tyr λβp 480 485 490 495 AGC AAC GTG GAG AGT GAT TCG GAC GAT GAC AGC GAT GCT AGT GGC GGC 1655 Ser Aβn Val Glu Ser λβp Ser Aβp Aβp Aβp Ser Aβp Ala Ser Gly Gly 500 505 510 GGA GGC GAC AGC GAC GGC GCC AAG AAA AAG AAG GAG AAG AAG TCC GAG 1703 Gly Gly λβp Ser λβp Gly Ala Lye Lye Lye Lye Glu Lye Lye Ser Glu 515 520 525 AAG AAA GAG AAA AAG GAG AAA AAA CAC AAG GAG AAG GAG AGA ACA λλG 1751 Lye Lye Glu Lye Lys Glu Lye Lys His Lys Glu Lys Glu λrg Thr Lys 530 535 540 AAA CCC TCC AAG AAG AAG AAG GAC TCT GGC AAA CCC AAG CGC GCC ACC 1799 Lys Pro Ser Lys Lye Lys Lys Asp Ser Gly Lys Pro Lye Arg Ala Thr 545 550 555 ACC GCT TTC ATG CTC TGG CTG AAC GAC ACG CGC GAG AGC ATC AAG AGG 1847 Thr Ala Phe Met Leu Trp Leu Asn Aβp Thr Arg Glu Ser He Lys Arg 560 565 570 575 GAA AAT CCG GGC ATA AAG GTT ACC GAG ATC GCC AAG AAG GGC GGC GAG 1895 Glu Asn Pro Gly He Lys Val Thr Glu He Ala Lye Lys Gly Gly Glu 580 585 590 ATG TGG AAG GAG CTG AAG GAC AAG TCC AAG TGG GAG GAT GCG GCG GCC 1943 Met Trp Lys Glu Leu Lys Asp Lye Ser Lye Trp Glu Aβp Ala λla λla 595 600 605 AAG GAC AAG CAG CGC TAC CAC GAC GAG ATG CGC AAC TAC AAG CCT GAA 1991 Lys Aβp Lys Gin λrg Tyr His Aβp Glu Met Arg Asn Tyr Lys Pro Glu 610 615 620 GCG GGC GGT GAC AGC GAC AAC GAG AAG GGT GGA AAG TCC TCC AAG AAG 2039 Ala Gly Gly λβp Ser Aβp Aβn Glu Lys Gly Gly Lye Ser Ser Lye Lye 625 630 635 CGC AAG ACG GAG CCT TCT CCA TCC AAG AAG GCG AAT ACC TCG GGC AGC 2087 Arg Lye Thr Glu Pro Ser Pro Ser Lys Lye Ala Asn Thr Ser Gly Ser 640 645 650 655 GGC TTC AAG AGC AAG GAG TAC ATT TCG GAC GAC GAC TCC ACC AGC TCC 2135 Gly Phe Lys Ser Lys Glu Tyr He Ser Aβp Aβp Aβp Ser Thr Ser Ser 660 665 670 GAC GAC GλG λλG GλC AAC GAG CCT GCC λλG λλG λλG λGC λλG CCC CCλ 2183 λβp λsp Glu Lys λsp λsn Glu Pro λla Lys Lys Lys Ser Lys Pro Pro 675 680 685 TCC GAC GGC GAT GCC AλG AAG AAA AλG GCC λλG λGC GλG λGC GAA CCG 2231 Ser Asp Gly λβp λla Lys Lys Lys Lys λla Lys Ser Glu Ser Glu Pro 690 695 700 GAG GAG AGC GλG GλG GλC λGC AAT GCC AGC GAT GAG GAT GAG GAA GAT 2279 Glu Glu Ser Glu Glu λsp Ser Aβn λla Ser λsp Glu λsp Glu Glu Asp 705 710 715 GAG GCC AGT GAT TAGGGCCATA AACACAACAA ATCAATTCCA TAAACACACA 2331 Glu λla Ser λβp CCACGCTCCT CACACACCCA TGTCCCAAAT CTAGTTTACA TTCGCCGGAA TTC 2384 (2) INFORMATION FOR SEQ ID NO:13 It (i) SEQUENCE CHARACTERISTICS: (λ) LENGTH: 723 amino acidβ (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (vi) ORIGINAL SOURCE: (A) ORGANISM: Drosophila melanogaβter (vii) IMMEDIATE SOURCE: (B) CLONE: Drosophila SSRP (predicted) (ix) FEATURE: (A) NAME/KEY: Domain (B) LOCATION: 458..507 (D) OTHER INFORMATION: /label= Acidic (ix) FEATURE: (A) NAME/KEY: Domain (B) LOCATION: 518..547 (D) OTHER INFORMATION: /label= Baβic I (ix) FEATURE: (A) NAME/KEY: Domain (B) LOCATION: 547..620 (D) OTHER INFORMATION: /label= HMG-box (ix) FEATURE: (A) NAME/KEY: Domain (B) LOCATION: 632..649 (D) OTHER INFORMATION: /label= Basic II (ix) FEATURE: (λ) NAME/KEY: Domain (B) LOCATION: 657..723 (D) OTHER INFORMATION: /label- Mixed Charge (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: Met Thr λβp Ser Leu Glu Tyr λβn λβp He λsn λla Glu Val λrg Gly 1 5 10 15 Val Leu Cyβ Ser Gly λrg Leu Lys Met Thr Glu G n λsn He He Phe 20 25 30 Lys λβn Thr Lye Thr Gly Lye Val Glu Gin He Ser λla Glu λβp He 35 40 45 λβp Leu He λβn Ser Gin Lys Phe Val Gly Thr Trp Gly Leu λrg Val 50 55 60 Phe Thr Lys Gly Gly Val Leu His Arg Phe Thr Gly Phe Arg Aβp Ser 65 70 75 80 Glu Hie Glu Lye Leu Gly Lye Phe He Lys Ala Ala Tyr Ser Gin Glu 85 90 95 Met Val Glu Lys Glu Met Cyβ Val Lye Gly Trp Aβn Trp Gly Thr Ala 100 105 110 Arg Phe Met Gly Ser Val Leu Ser Phe Aep Lye Glu Ser Lye Thr He 115 120 125 Phe Glu Val Pro Leu Ser Hie Val Ser Gin Cyβ Val Thr Gly Lye Aβn 130 135 140 Glu Val Thr Leu Glu Phe Hie Gin Asn Aβp Aβp Ala Pro Val Gly Leu 145 150 155 160 Leu Glu Met Arg Phe His He Pro Ala Val Glu Ser λla Glu Glu λsp 165 170 175 Pro Val λsp Lye Phe His Gin Aen Val Met Ser Lye Ala Ser Val He 180 185 190 Ser Ala Ser Gly Glu Ser He Ala He Phe Arg Glu He Gin He Leu 195 200 205 Thr Pro Arg Gly Arg Tyr Asp He Lys He Phe Ser Thr Phe Phe Gin 210 215 220 Leu His Gly Lys Thr Phe Asp Tyr Lye He Pro Met Asp Ser Val Leu 225 230 235 240 Arg Leu Phe Met Leu Pro His Lye λsp Ser λrg Gin Met Phe Phe Val 245 250 255 Leu Ser Leu λsp Pro Pro He Lys Gin Gly Gin Thr λrg Tyr Hie Tyr 260 265 270 Leu Val Leu Leu Phe Ala Pro Asp Glu Glu Thr Thr He Glu Leu Pro 275 280 285 Phe Ser Glu Ala Glu Leu Arg Asp Lys Tyr Glu Gly Lys Leu Glu Lye 290 295 300 Glu He Ser Gly Pro Val Tyr Glu Val Met Gly Lye Val Met Lys Val 305 310 315 320 Leu He Gly λrg Lys He Thr Gly Pro Gly Aβn Phe He Gly His Ser 325 330 335 Gly Thr λla λla Val Gly Cyβ Ser Phe Lys λla λla λla Gly Tyr Leu 340 345 350 Tyr Pro Leu Glu λrg Gly Phe He Tyr He His Lye Pro Pro Leu His 355 360 365 He λrg Phe Glu Glu He Ser Ser Val λsn Phe λla λrg Ser Gly Gly 370 375 380 Ser Thr Arg Ser Phe Asp Phe Glu Val Thr Leu Lys Asn Gly Thr Val 385 390 395 400 His He Phe Ser Ser He Glu Lys Glu Glu Tyr Ala Lys Leu Phe Aep 405 410 415 Tyr He Thr Gin Lye Lye Leu His Val Ser Aβn Met Gly Lys Asp Lys 420 425 430 Ser Gly Tyr Lys Aβp Val λsp Phe Gly Aep Ser Aβp Aβn Glu Aβn Glu 435 440 445 Pro Aβp Ala Tyr Leu Ala Arg Leu Lye Ala Glu Ala Arg Glu Lye Glu 450 455 460 Glu Aβp Asp Asp Aβp Gly Aβp Ser Aβp Glu Glu Ser Thr Asp Glu Asp 465 470 475 480 Phe Lye Pro Aβn Glu Aβn Glu Ser Asp Val Ala Glu Glu Tyr Asp Ser 485 490 495 Aβn Val Glu Ser Asp Ser Asp Asp Asp Ser Aep Ala Ser Gly Gly Gly 500 505 510 Gly Asp Ser Aβp Gly Ala Lys Lys Lye Lys Glu Lys Lys Ser Glu Lys 515 520 525 Lye Glu Lys Lys Glu Lys Lys His Lys Glu Lys Glu Arg Thr Lys Lys 530 535 540 Pro Ser Lys Lys Lys Lys Aβp Ser Gly Lys Pro Lye Arg Ala Thr Thr 545 550 555 560 Ala Phe Met Leu Trp Leu Asn Aβp Thr Arg Glu Ser He Lye Arg Glu 565 570 575 Asn Pro Gly He Lye Val Thr Glu He Ala Lye Lye Gly Gly Glu Met 580 585 590 Trp Lye Glu Leu Lys Asp Lys Ser Lys Trp Glu Asp Ala Ala Ala Lys 595 600 605 Asp Lys Gin Arg Tyr Hie Asp Glu Met Arg Asn Tyr Lys Pro Glu Ala 610 615 620 Gly Gly λsp Ser λβp λβn Glu Lye Gly Gly Lye Ser Ser Lye Lye λrg 625 630 635 640 Lye Thr Glu Pro Ser Pro Ser Lys Lys Ala Asn Thr Ser Gly Ser Gly 645 650 655 Phe Lys Ser Lys Glu Tyr He Ser Asp λsp λsp Ser Thr Ser Ser λβp 660 665 670 λsp Glu Lys Asp Asn Glu Pro λla Lye Lye Lye Ser Lye Pro Pro Ser 675 680 685 λβp Gly λβp λla Lys Lys Lys Lys λla Lys Ser Glu Ser Glu Pro Glu 690 695 700 Glu Ser Glu Glu Asp Ser Aβn λla Ser λβp Glu Aep Glu Glu Asp Glu 705 710 715 720 (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3292 baβe pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (vi) ORIGINAL SOURCE: (A) ORGANISM: Saccharomyces cereviβiae (vii) IMMEDIATE SOURCE: (B) CLONE: lambda yPt (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..1626 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: GAA TTC GGG TTT CAA GCC CAG CCT CAA CAA CAA CAA CAG CAG CAG CAG 48 Glu Phe Gly Phe Gin Ala Gin Pro Gin Gin Gin Gin Gin Gin Gin Gin 1 5 10 15 CAA CAA CAG CAA CAA CAA CAA GCG CCT TAT CAA GGT CAC TTC CAG CAG 96 Gin Gin Gin Gin Gin Gin Gin Ala Pro Tyr Gin Gly Hie Phe Gin Gin 20 25 30 TCG CCT CAA CAA CAA CAG CAA AAT GTT TAT TTT CCA CTA CCT CCA CAA 144 Ser Pro Gin Gin Gin Gin Gin Aen Val Tyr Phe Pro Leu Pro Pro Gin 35 40 45 TCT TTG ACG CAA CCT ACT TCG CAG TCG CAA CAA CAA CAA CAA CAG TAT 192 Ser Leu Thr Gin Pro Thr Ser Gin Ser Gin Gin Gin Gin Gin Gin Tyr 50 55 60 GCT AAT TCG AAC TCA AAT TCA AAC AAC AAT GTT AAT GTT AAC GCG CTA 240 Ala Asn Ser Asn Ser Asn Ser Aen Aεn Aεn Val Asn Val Asn Ala Leu 65 70 75 80 CCT CAG GAT TTC GGT TAC ATG CAA CAA ACC GGA TCG GGC CAA AAC TAT 288 Pro Gin Aβp Phe Gly Tyr Met Gin Gin Thr Gly Ser Gly Gin λβn Tyr 85 90 95 CCG ACG ATC AAT CAA CAA CAA TTT TCC GAG TTT TAC AAC TCC TTT TTA 336 Pro Thr He Aβn Gin Gin Gin Phe Ser Glu Phe Tyr λβn Ser Phe Leu 100 105 110 AGT CAT TTλ ACT CAA AAA CAG λCλ AAC CCT TCT GTC ACG GGT ACA GGC 384 Ser Hie Leu Thr Gin Lys Gin Thr Asn Pro Ser Val Thr Gly Thr Gly 115 120 125 GCG TCT AGT AAC AAC AAC AGT AAC AAC AAC AAT GTT AGT AGC GGC AAT 432 λla Ser Ser λsn λsn λβn Ser λβn λβn λβn λβn Val Ser Ser Gly λβn 130 135 140 AAC AGC ACT AGC AGT AAT CCT ACC CAG CTG GCA GCC TCC CAA TTA AAC 480 Asn Ser Thr Ser Ser Asn Pro Thr Gin Leu Ala Ala Ser Gin Leu Asn 145 150 155 160 CCT GCC ACG GCT ACT ACG GCC GCC GCA AAC AAT GCT GCT GGC CCG GCT 528 Pro Ala Thr Ala Thr Thr Ala Ala Ala Aen Aβn Ala Ala Gly Pro Ala 165 170 175 TCG TAC TTG TCT CAG CTC CCA CAG GTG CAG AGA TAC TAC CCG AAC AAC 576 Ser Tyr Leu Ser Gin Leu Pro Gin Val Gin Arg Tyr Tyr Pro λβn Aβn 180 185 190 ATG AλC GCT CTG TCT λGT CTT TTG GAC CCT TCC TCT GCA GGA AλT GCT 624 Met λβn λla Leu Ser Ser Leu Leu Aβp Pro Ser Ser Ala Gly λsn Ala 195 200 205 GCA GGA AAT GCC AAC ACC GCT ACT CAT CCT GGT TTG TTA CCA CCC AAT 672 Ala Gly Asn Ala Asn Thr Ala Thr His Pro Gly Leu Leu Pro Pro Aβn 210 215 220 CTG CAA CCT CAA TTG ACT CAC CAC CAG CAG CAG ATG CAG CAA CAG CTG 720 Leu Gin Pro Gin Leu Thr Hie His Gin Gin Gin Met Gin Gin Gin Leu 225 230 235 240 CAA TTA CAA CAA CAA CAG CAG TTG CAG CAA CAG CAG CAG CTA CAA CAG 768 Gin Leu Gin Gin Gin Gin Gin Leu Gin Gin Gin Gin Gin Leu Gin Gin 245 250 255 CAA CAC CAG TTG CAA CAA CAA CAA CAA CTT CAA CAA CAA CAT CAT CAT 816 Gin His Gin Leu Gin Gin Gin Gin Gin Leu Gin Gin Gin Hie Hie Hie 260 265 270 CTA CAA CAG CAA CAG CAG CAA CAA CAG CAT CCA GTG GTG AAG AAA TTA 864 Leu Gin Gin Gin Gin Gin Gin Gin Gin Hie Pro Val Val Lye Lye Leu 275 280 285 TCT TCC ACT CAA AGC AGA ATT GAG AGA AGA AAA CAA CTG AAA AAG CAA 912 Ser Ser Thr Gin Ser Arg He Glu Arg Arg Lye Gin Leu Lye Lys Gin 290 295 300 GGC CCA AλG λGA CCT TCT TCC GCT TAT TTC CTG TTT TCT ATG TCC ATA 960 Gly Pro Lye Arg Pro Ser Ser Ala Tyr Phe Leu Phe Ser Met Ser He 305 310 315 320 AGA AAT GAG TTG CTT Cλλ CAA TTC CCT GAA GCA AAG GTC CCC GAA TTG 1008 λrg λβn Glu Leu Leu Gin Gin Phe Pro Glu λla Lys Val Pro Glu Leu 325 330 335 TCT AAA TTG GCT TCT GCA AGG TGG AAA GAG TTA ACG GAT GAT Cλλ AAA 1056 Ser Lys Leu λla Ser λla λrg Trp Lye Glu Leu Thr λsp λβp Gin Lye 340 345 350 AAA CCλ TTC TλC GAA GAA TTC AGA ACC AAC TGG GAG λλG TλC AGA GTT 1104 Lye Pro Phe Tyr Glu Glu Phe λrg Thr λβn Trp Glu Lye Tyr λrg Val 355 360 365 GTG AGA GAT GCT TλC GAA λλG ACT TTG CCC CCA λλG λGA CCC TCT GGT 1152 Val λrg λβp λla Tyr Glu Lye Thr Leu Pro Pro Lye λrg Pro Ser Gly 370 375 380 CCC TTT λTT CλG TTC λCC CλG GAG ATT AGλ CCT λCC GTC GTC AAG Gλλ 1200 Pro Phe He Gin Phe Thr Gin Glu He Arg Pro Thr Val Val Lye Glu 385 390 395 400 AAT CCT GAT AAA GGT TTA ATC GAA ATT ACC AAG ATA ATC GGT GAA AGA 1248 Aβn Pro λβp Lye Gly Leu He Glu He Thr Lys He He Gly Glu Arg 405 410 415 TGG CGC GAG TTA GAC CCC TGC CAA AAG GCG GAA TAC ACT GAA ACT TAC 1296 Trp λrg Glu Leu Asp Pro Cyβ Gin Lye Ala Glu Tyr Thr Glu Thr Tyr 420 425 430 AAG AAA AGA TTA AAG GAA TGG GAA AGT TGT TAT CCC GAC GAA AAT GAT 1344 Lys Lys λrg Leu Lye Glu Trp Glu Ser Cyβ Tyr Pro λβp Glu λβn Asp 435 440 445 CCA AAC GGT AAC CCA ACC GGT CAC TCA CAT AAG GCC ATG AAC ATG AAT 1392 Pro Asn Gly λsn Pro Thr Gly His Ser Hie Lye λla Met λβn Met λβn 450 455 460 TTG AAT ATG GAC ACT AAA ATC ATG GAG AAC CAA GAC AGT ATC GAG CAC 1440 Leu Aβn Met Aβp Thr Lys He Met Glu Asn Gin Aβp Ser He Glu His 465 470 475 480 ATA ACC GCA AAT GCC ATC GAC TCA GTT ACC GGA AGC AAC AGT AAC AGT 1488 He Thr Ala Aβn Ala He Aβp Ser Val Thr Gly Ser Aβn Ser Asn Ser . 485 490 495 ACC ACC CCA AAT ACG CCC GTT TCT CCT CCG ATT TCA TTA CAG CAG CAG 1536 Thr Thr Pro Aβn Thr Pro Val Ser Pro Pro He Ser Leu Gin Gin Gin 500 505 510 CCG CTC CAA CAA CAA CAA CAA CAG CAG CAA CAA CAA CAA CAC ATG TTA 1584 Pro Leu Gin Gin Gin Gin Gin Gin Gin Gin Gin Gin Gin His Met Leu 515 520 525 TTG GCT GAC CCC ACT ACA AAT GGT TCG ATC ATA AAA AAT GAA 1626 Leu Ala Asp Pro Thr Thr Aεn Gly Ser He He Lye Aεn Glu 530 535 540 TAACAAATAA ACAACTTTAG TTTTCCACTG TAACATTATC CGACGCAAAC AACGAGAATA 1686 AGGAATTCGA ATTCCTTTTT CAACATTTGT TTAATATTGT ACTACTCTAT TTCCTATTAC 1746 TACAAATTTT ACTTTATTTA ATAATAATTT TTCTTTCCCT TTTTCTAACT TCAGTCTATA 1806 TGTATTTGCC TGTATλCλTλ TλCGCλTGTG TGTλGTCTTC CCTCCTTCTT GTTTTTGTAA 1866 TATλCTTλλG CCλλATTCAA GTTTGCCTCT GλTGCTGTGC GλGCTCAACT GλCGλGCGTG 1926 ATGAAGCCAA λλλλλTTAAT TGATTTCGCC CλGATCGλλC TGGGGATCTG CTGCGTGTTλ 1986 λGCAGATCCA TAGCGλCTλG λCCACGAAAC CTATTλλTCT GTλAAATTGA TCATTTTλAA 2046 GTGGCATAGT TGTACGATAC ACAAGGGCGA CTTATCλλCT TACλCATλλλ TATGTTTGAA 2106 ACATGTCAGA AACACTCGTT λCAAAGCAGA CAAAATTTAT TACλTCλλλC GλTACCCTGC 2166 CTAGλCλλλC CAGTTAAACG TTGTAAATAC CTGGACAACT λGTTTλGTTC CGAGATTCTG 2226 CGCTTCCλTT GAGTCTTATG ACTGTTTCTC λGTTTTCATG TCATCTTTTG λCGCCGCATG 2286 GGATAATGTG TACTAATAAC ATλAATACTA GTCAATAGλT GATλTTλCGλ TTCCATCCλC 2346 λAAGGTGAGG TGCTAGTCAC CACCTAAGGA TATTAGATTG TCAAGATGCC CGCTATTACT 2406 GGλGCCCTTA GTATAACGGA TATTTTCAGG ATAGCAGACT TACTTCTCCA AGTGTλλGGG 2466 λACACCGAAT CTAAAGTAGC TACTGCTCCT CCATTCCGTG TATATAATCT TGCTTTTTTT 2526 TAGGAAAATA CTAATACTCG CATATATTGG TTATTATCAT TACTTGGACA CTGTCTGTTC 2586 TATCGCTTCA TTTGTAATAT GCGTATTGCC CTTCTTATTA ATTGGCTAAT ATTTCλCCTG 2646 CAACATAGGT CCCTGTTGAT TAACGTGTTT ATCCATTTCA ATCATGAGAA ATGTTTCTTC 2706 TGTTTTCCAA TGCCTGGCCG AGCTGGTAAT ATATATATAT ATATGTACAT λATACTTTλT 2766 TAGATATATT GTTGATGATT AGTAGACAAG TGGTACTACC AACCGAGAAT AAAAGCTGGT 2826 CTTCTTATAT AATATGAGTA TGGTATAAAT AGCAGTCACC GATATCATTG GTTACCCAAA 2886 GTGACAATTC λTGTCTTTCA TAGATATAAA TCGTAAGCTA AAATTGAATT AAAAGATCTT 2946 TAATTTAGCT GCCCTGCTAA TCTGAAGTCA CATATCATTC CTCATTCTGG ATCACTCACA 3006 ACATTTATTG TCTAATAACT TATGTAATCA CTATAGTCAC TGGTGTGAAC AATGTGAGCA 3066 ATAATAAACC ACTGTATTAC CATATACAAA TGCATATGTT TAGCCACATA AGTTTAATTT 3126 ATλTTTCTTA TTTTCCACAC GATATCCCCA CTATCAATGA CATAGATGAT ATTTTCTCCA 3186 CTGGAACAAC CTGAATACAA CAATATATTA TTTGTTCAAG TACCGCTTCA GAAATTAAAT 3246 λCTCTGTAAT TTTGACCCCT TCTAGCACCA TATGTACCCC GAATTC 3292 (2) INFORMATION FOR SEQ ID NO: 13 : (i) SEQUENCE CHARACTERISTICS : (A) LENGTH: 542 amino acids (B ) TYPEs amino acid (D ) TOPOLOGY: linear (ii) MOLECULE TYPE : peptide (vi) ORIGINAL SOURCE: (A) ORGANISM: Saccharomyces cerevisiae (vii) IMMEDIATE SOURCE: (B) CLONE: fractional yeaβt SSRP (fySSRP) (predicted) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: Glu Phe Gly Phe Gin λla Gin Pro Gin Gin Gin Gin Gin Gin Gin Gin 1 5 10 15 Gin Gin Gin Gin Gin Gin Gin λla Pro Tyr Gin Gly Hie Phe Gin Gin 20 25 30 Ser Pro Gin Gin Gin Gin Gin λβn Val Tyr Phe Pro Leu Pro Pro Gin 35 40 45 Ser Leu Thr Gin Pro Thr Ser Gin Ser Gin Gin Gin Gin Gin Gin Tyr 50 55 60 λla λβn Ser λβn Ser Aen Ser Asn Asn Aen Val Asn Val λβn λla Leu 65 70 75 80 Pro Gin Asp Phe Gly Tyr Met Gin Gin Thr Gly Ser Gly Gin Aβn Tyr 85 90 95 Pro Thr He λβn Gin Gin Gin Phe Ser Glu Phe Tyr λβn Ser Phe Leu 100 105 110 Ser Hie Leu Thr Gin Lye Gin Thr Aen Pro Ser Val Thr Gly Thr Gly 115 120 125 λla Ser Ser λεn λβn λβn Ser Asn Aβn Aβn Asn Val Ser Ser Gly Asn 130 135 140 λsn Ser Thr Ser Ser Aβn Pro Thr Gin Leu Ala Ala Ser Gin Leu Aβn 145 150 155 160 Pro Ala Thr Ala Thr Thr Ala Ala Ala Aεn Aen Ala Ala Gly Pro Ala 165 170 175 Ser Tyr Leu Ser Gin Leu Pro Gin Val Gin Arg Tyr Tyr Pro Asn Asn 180 185 190 Met Aεn -Ala Leu Ser Ser Leu Leu Asp Pro Ser Ser Ala Gly Asn Ala 195 200 205 λla Gly λsn λla λsn Thr λla Thr His Pro Gly Leu Leu Pro Pro λβn 210 215 220 Leu Gin Pro Gin Leu Thr Hie His Gin Gin Gin Met Gin Gin Gin Leu 225 230 235 240 Gin Leu Gin Gin Gin Gin Gin Leu Gin Gin Gin Gin Gin Leu Gin Gin 245 250 255 Gin His Gin Leu Gin Gin Gin Gin Gin Leu Gin Gin Gin Hie Hie Hie 260 265 270 Leu Gin Gin Gin Gin Gin Gin Gin Gin Hiε Pro Val Val Lyε Lys Leu 275 280 285 Ser Ser Thr Gin Ser λrg He Glu Arg Arg Lys Gin Leu Lys Lyε Gin 290 295 300 Gly Pro Lye λrg Pro Ser Ser λla Tyr Phe Leu Phe Ser Met Ser He 305 310 315 320 λrg λβn Glu Leu Leu Gin Gin Phe Pro Glu λla Lye Val Pro Glu Leu 325 330 335 Ser Ly* Leu λla Ser λla λrg Trp Lys Glu Leu Thr λsp λβp Gin Lye 340 345 350 Lys Pro Phe Tyr Glu Glu Phe λrg Thr λβn Trp Glu Lys Tyr λrg Val 355 360 365 Val λrg λβp Ala Tyr Glu Lye Thr Leu Pro Pro Lye Arg Pro Ser Gly 370 375 380 Pro Phe He Gin Phe Thr Gin Glu He Arg Pro Thr Val Val Lye Glu 385 390 395 400 Asn Pro Aβp Lye Gly Leu He Glu He Thr Lys He He Gly Glu Arg 405 410 415 Trp Arg Glu Leu Asp Pro Ala Lyε Lyε Ala Glu Tyr Thr Glu Thr Tyr 420 425 430 Lye Lye Arg Leu Lys Glu Trp Glu Ser Cys Tyr Pro Aβp Glu λsn λβp 435 440 445 Pro Aβn Gly Aβn Pro Thr Gly Hie Ser Hiε Lye Ala Met Aβn Met Aβn 450 455 460 Leu λβn Met λβp Thr Lys He Met Glu Asn Gin Asp Ser He Glu His 465 470 475 480 He Thr Ala Aβn Ala He Aβp Ser Val Thr Gly Ser Asn Ser Aβn Ser 485 490 495 Thr Aβn Pro Asn Thr Pro Val Ser Pro Pro He Ser Leu Gin Gin Gin 500 505 510 Pro Leu Gin Gin Gin Gin Gin Gin Gin Gin Gin Gin Gin His Met Leu 515 520 525 Leu Ala Asp Pro Thr Thr Asn Gly Ser He He Lyε Asn Glu 530 535 540

Claims: CLAIMS 1. A method of identifying cDNA encoding a eukaryotic DNA structure specific recognition protein from a cDNA expression library prepared from eukaryotic cells, comprising the steps of: (a) preparing at least one oligonucleotide probe, the probe comprising at least one DNA structural motif of a predetermined type, and a detectable label; (b) screening the expression products of the cDNA expression library with the probe of (a) ; (c) detecting the presence of an expresεion product which selectively binds to the probe of (a) ; and (d) identifying the cDNA source of the expresεion product of (c) . 2. cDNA encoding a eukaryotic DNA structure specific recognition protein identified according to the method of Claim 1. 3. . A eukaryotic DNA structure specific recognition protein encoded by the cDNA of Claim 2. 4. A method of Claim 1 wherein the DNA εtructural motif present in the oligonucleotide probe comprises a 1,2- intraεtrand dinucleotide adduct. 5. A method of Claim 1 wherein the DNA εtructural motif preεent in the oligonucleotide probe iε a DNA adduct of a therapeutically active platinum compound. 6. A method of Claim 5 wherein the platinum compound is cisplatin. 7. A DNA structure specific recognition protein which selectively bindε to a double-εtranded DNA fragment having at leaεt one region of DNA damage compriεing a 1,2-intrastrand dinucleotide adduct to form a (damaged DNA fragment) : (protein) complex, which haε a retarded electrophoretic mobility relative to the mobility of the damaged DNA fragment alone. 8. A DNA εtructure εpecific recognition protein of Claim 7, further characterized in that it haε the property, when affixed to a εolid εupport, of binding εelectively to said damaged DNA fragment and not to a double-stranded DNA fragment lacking said 1,2- intrastrand dinucleotide adduct. 9. An active protein preparation comprising the DNA εtructure εpecific recognition protein of Claim 8, wherein the 1,2-intraεtrand dinucleotide adduct iε a DNA adduct of a therapeutically active platinum compound. 10. An active protein preparation of Claim 9 wherein the platinum compound iε cisplatin. 11. An active protein preparation of Claim 9, comprising an extract of whole eukaryotic cells, an extract of eukaryotic cell cytoεol, or an extract of eukaryotic cell nuclei. 12. An active protein preparation of Claim 11, wherein the eukaryotic cellε are of human origin. 13. An active protein preparation of Claim 9, derived from human cells by: (a) preparing an extract of whole cells, an extract of cell cytosol, or an extract of cell nuclei; and - Ill - (b) obtaining a fraction of the extract of (a) which consiεts essentially of proteins which are soluble in a solution 45% saturated with ammonium sulfate, and insoluble in a solution 65% saturated with ammonium sulfate. 14. An active protein preparation of Claim 11, wherein the eukaryotic cells are of Droεophila melanogaster origin. 15. An active protein preparation of Claim 11, wherein the eukaryotic cells are of Saccharomyceε cereveεiae origin. 16. A eukaryotic DNA structure εpecific recognition protein having the propertieε of: (a) εelective binding to a double-εtranded DNA fragment having at least one region of DNA damage comprising a 1,2-intrastrand dinucleotide adduct, including the l,2-d(ApG) and l,2-d(GpG) diadducts of cisplatin, to form a (damaged DNA fragment) : (protein) complex which haε a retarded electrophoretic mobility relative to the mobility of the damaged DNA fragment alone; (b) when affixed to a εolid εupport, εaid protein bindε εelectively to a double-εtranded DNA fragment having at least one region of DNA damage comprising a 1,2-intrastrand dinucleotide adduct, and not to a double-εtranded DNA fragment lacking εaid region of DNA damage; (c) εedimentation through a εucroεe gradient with a coefficient of about 5.6S; and (d) SDS-PAGE electrophoretic mobility corresponding to an apparent molecular weight of about 91,000 daltons. 17. An antibody selectively reactive with the eukaryotic DNA εtructure εpecific recognition protein of Claim 16. 18. Isolated RNA of eukaryotic origin which encodes the eukaryotic DNA structure εpecific recognition protein of Claim 16, or which iε substantially homologous with all or at least a region of the RNA encoding said eukaryotic DNA εtructure εpecific recognition protein. 19. Iεolated DNA encoding all or at leaεt a portion of human DNA εtructure εpecific recognition protein. 20. Iεolated DNA having a nucleotide sequence selected from the group consisting of: (a) all or at least a portion of SEQ ID No. 6; (b) a sequence εubεtantially homologouε to all or at leaεt a portion of SEQ ID No. 6; (c) all or at least a region of the nucleotide εequence of the λPtl gene; (d) all or at least a region of the nucleotide sequence of the λPt2 gene; (e) a sequence substantially homologous to all or at least a region of the nucleotide sequence of the λPtl gene; (f) a εequence εubstantially homologous to all or at leaεt a region of the nucleotide εequence of the λPt2 gene; (g) all or at least a portion of SEQ ID No. 8; (h) all or at least a portion of SEQ ID No. 9; (i) a εequence substantially homologous to all or at least a region of SEQ ID No. 8; (j) a sequence substantially homologous to all or at least a region of SEQ ID No. 9; and (k) all or at least a region of the λPtl gene present in E. coli recombinant cellε, ATCC Depoεit No. 40498. 21. Iεolated DNA encoding all or at leaεt a portion of Droεophila melanogaεter DNA εtructure specific recognition protein. 22. Isolated DNA having a nucleotide sequence selected from the group consisting of: (a) all or at least a portion of SEQ ID No. 10; and (b) a sequence substantially homologous to all or at least a portion of SEQ ID No. 10. 23. Iεolated DNA encoding all or at least a portion of Saccharomyceε cereviεiae DNA structure εpecific recognition protein. 24. Iεolated DNA having a nucleotide εequence εelected from the group consisting of: (a) all or at least a region of the nucleotide sequence of the λyPt gene; (b) a sequence substantially homologous to all or at least a region of the nucleotide sequence of the λyPt gene; (c) all or at least a portion of SEQ ID No. 12; and (d) a sequence substantially homologous to all or at least a portion of SEQ ID No. 12. 25. A nucleotide probe capable of hybridizing to a nucleotide sequence selected from the group consiεting of: (a) all or at least a region of cDNA encoding human DNA structure εpecific recognition protein; (b) a nucleotide sequence having substantial homology to all or at least a region of cDNA encoding human DNA structure specific recognition protein; (c) all or at leaεt a portion of SEQ ID No. 6; (d) a nucleotide εequence having εubεtantial homology to all or at leaεt a portion of SEQ ID No. 6; (e) all or at leaεt a region of the nucleotide sequence of the λPtl gene; (f) all or at leaεt a region of the nucleotide εequence of the λPt2 gene; (g) a nucleotide εequence having εubεtantial homology to all or at leaεt a region of the nucleotide εequence of the λPtl gene; (h) a nucleotide εequence having εubεtantial homology to all or at least a region of the nucleotide sequence of the λPt2 gene; (i) all or at least a region of the nucleotide sequence of SEQ ID No. 8; (j) all or at least a region of the nucleotide sequence of SEQ ID No. 9; (k) a nucleotide sequence having subεtantial homology to to the nucleotide εequence of SEQ ID No. 8; (1) a nucleotide εequence having εubstantial homology to to the nucleotide sequence of SEQ ID No. 9; (m) all or at least a region of the λPtl gene present in E. coli recombinant cells, ATCC Deposit No. 40498. 26. A nucleotide probe capable of hybridizing to a nucleotide sequence selected from the group consiεting of: (a) all or at leaεt a region of cDNA encoding Droεophila melanogaεter DNA structure specific recognition protein; (b) a nucleotide sequence having subεtantial homology to all or at least a region of cDNA encoding Drosophila melanogaεter DNA εtructure specific recognition protein; (c) all or at least a portion of SEQ ID No. 10; and (d) a nucleotide sequence having substantial homology to all or at least a portion of SEQ ID No. 10. 27. A nucleotide probe capable of hybridizing to a nucleotide sequence selected from the group consisting of: (a) all or at least a region of cDNA encoding Saccharomyceε cereveεiae DNA structure specific recognition protein; (b) a nucleotide sequence having subεtantial homology to all or at least a region of cDNA encoding Saccharomyces cereveεiae DNA structure specific recognition protein; (c) all or at least a portion of SEQ ID No. 12; and (d) a nucleotide sequence having subεtantial homology to all or at least a portion of SEQ ID No. 12. 28. A recombinant protein having DNA structure specific recognition activity, encoded by a nucleotide sequence selected from the group consisting of: (a) all or at least a portion of SEQ ID No. 6; (b) a nucleic acid εequence εubstantially homologous to all or at least a portion of SEQ ID No. 6; (c) all or at least a portion of SEQ ID No. 8; (d) all or at least a portion of SEQ ID No. 9; (e) a nucleic acid sequence εubstantially homologous to all or at least a portion of SEQ ID No. 8; (f) a nucleic acid sequence substantially homologous to all or at least a portion of SEQ ID No. 9; and (g) all or at least a portion of the λPtl gene present in E. coli recombinant cellε, ATCC Deposit No. 40498. 29. A recombinant protein having DNA structure specific recognition activity, comprising all or at least a region of the amino acid sequence of SEQ ID No. 7. 30. A recombinant protein having DNA εtructure specific recognition activity, comprising all or at least a εubstantial portion of the amino acid sequence of the HMG-box domain region of SEQ ID No. 7. 31. An antibody selectively reactive with a DNA εtructure εpecific recognition protein selected from the group consisting of: (a) a recombinant protein having DNA structure specific recognition activity, encoded by all or at leaεt a region of the nucleotide εequence of SEQ ID No. 6; (b) a recombinant protein having DNA εtructure εpecific recognition activity, encoded by all or at leaεt a region of a nucleotide εequence εubstantially homologous to the nucleotide sequence of SEQ ID No. 6; (c) a recombinant protein having DNA structure εpecific recognition activity, encoded by all or at least a region of the nucleotide εequence of SEQ ID No. 8; (d) a recombinant protein having DNA εtructure specific recognition activity, encoded by all or at least a region of a nucleotide sequence εubstantially homologous to the nucleotide sequence of SEQ ID No. 8; (e) a recombinant protein having DNA structure specific recognition activity, encoded by all or at least a region of the nucleotide sequence of SEQ ID No. 9; (f) a recombinant protein having DNA structure specific recognition activity, encoded by all or at leaεt a region of a nucleotide sequence substantially homologous to the nucleotide sequence of SEQ ID No. 9; (g) a recombinant protein having DNA εtructure εpecific recognition activity, encoded by all or at least a region of the λPtl gene present in E. coli recombinant cells, ATCC Depoεit No. 40498; (h) a recombinant protein encoded by DNA having substantial homology to all or at least a region of the λPtl gene present in E. coli recombinant cells, ATCC Deposit No. 40498; (i) a recombinant protein comprising all or at least a region of the amino acid sequence of SEQ ID No. 7; and (j) a recombinant protein comprising all or at least a εubstantial portion of the amino acid sequence of the HMG-box domain region of SEQ ID No. 7. 32. A recombinant protein having DNA structure specific recognition activity, encoded by a nucleic acid sequence selected from the group consisting of: (a) all or at least a portion of SEQ ID No. 10; and (b) a nucleic acid sequence substantially homologous to all or at least a region of the nucleotide εequence of SEQ ID No. 10. 33. A recombinant protein having DNA εtructure specific recognition activity, comprising all or at leaεt a region of the amino acid εequence of SEQ ID No. 11. 34. A recombinant protein having DNA εtructure εpecific recognition activity, comprising all or at least a εubεtantial portion of the amino acid εequence of the HMG-box domain region of SEQ ID No. 11. 35. An antibody εelectively reactive with a DNA εtructure εpecific recognition protein εelected from the group conεisting of: (a) a recombinant protein having DNA structure specific recognition activity, encoded by all or at least a region of the nucleotide εequence of SEQ ID No. 10; (b) a recombinant protein having DNA structure εpecific recognition activity, encoded by all or at least a region of a nucleotide sequence subεtantially homologous to the nucleotide sequence of SEQ ID No. 10; (c) a recombinant protein comprising all or at least a region of the amino acid sequence of SEQ ID No. 11; and (d) a recombinant protein comprising all or at least a subεtantial portion of the amino acid εequence of the HMG-box domain region of SEQ ID No. 11. 36. A recombinant protein having DNA structure specific recognition activity, a substantial portion of which is encoded by a nucleotide sequence selected from the group consiεting of: (a) the λyPt gene; (b) all or at leaεt a region of the nucleotide εequence of SEQ ID No. 12; and (c) a nucleic acid εequence εubstantially homologous to all or at least a region of the nucleotide sequence of SEQ ID No. 12. 37. A recombinant protein having DNA structure specific recognition activity, comprising at least all or a region of the amino acid sequence of SEQ ID No. 13. 38. A recombinant protein having DNA structure specific recognition activity, comprising at least all or a region of the amino acid sequence of fySSRP. 39. An antibody selectively reactive with a DNA structure specific recognition protein selected from the group conεiεting of: (a) a recombinant protein having DNA structure specific recognition activity, a substantial portion of which iε encoded by the λyPt gene; (b) a recombinant protein having DNA εtructure specific recognition activity, a substantial portion of which is encoded by all or at least a region of the nucleotide sequence of SEQ ID No. 12; (c) a recombinant protein having DNA structure specific recognition activity, a subεtantial portion of which iε encoded by a nucleic acid εequence substantially homologous to all or at least a region of the nucleotide sequence of SEQ ID No. 12; (d) a recombinant protein having DNA structure specific recognition activity, comprising at least all or a region of the amino acid sequence of fySSRP; and (e) a recombinant protein having DNA structure εpecific recognition acitivy, compriεing at least all or a region of the amino acid εequence of SEQ ID No. 13. 40. A method of detecting DNA εtructure εpecific recognition protein in eukaryotic cellε, compriεing the εteps of: (a) treating eukaryotic cells in such a manner as to produce an extract containing DNA from the cells; (b) contacting the extract produced in (a) with a nucleotide probe capable of hybridizing to all or at leaεt a region of cellular DNA encoding DNA structure specific recognition protein; and (c) detecting hybridization. 41. A method of Claim 40 wherein the nucleotide probe iε capable of hybridizing to a nucleotide sequence selected from the group conεiεting of: (a) all or at leaεt a region of cDNA encoding human DNA εtructure specific recognition protein; (b) a nucleotide sequence having subεtantial homology to all or at least a region of cDNA encoding human DNA structure specific recognition protein; (c) all or at least a portion of SEQ ID No. 6; (d) a nucleotide sequence having substantial homology to all or at least a portion of SEQ ID No. 6; (e) all or at leaεt a region of the nucleotide εequence of the λPtl gene; (f) all or at leaεt a region of the nucleotide εequence of the λPt2 gene; (g) a nucleotide εequence having εubεtantial homology to all or at least a region of the nucleotide sequence of the λPtl gene; _ (h) a nucleotide εequence having εubεtantial homology to all or at leaεt a region of the nucleotide εequence of the λPt2 gene; (i) all or at leaεt a region of the nucleotide εequence of SEQ ID No. 8; (j) all or at least a region of the nucleotide sequence of SEQ ID No. 9; (k) a nucleotide sequence having substantial homology to to the nucleotide sequence of SEQ ID No. 8; (1) a nucleotide sequence having εubstantial homology to to the nucleotide sequence of SEQ ID No. 9; ( ) all or at least a region of the λPtl gene present in E. coli recombinant cells, ATCC Deposit No. 40498. 42. A method of Claim 41 wherein the eukaryotic cellε are human cellε. 43. A method of detecting, in eukaryotic cellε, a DNA εtructure εpecific recognition protein which εelectively binds to a DNA εtructural motif comprising a 1,2-intrastrand dinucleotide adduct, the method compriεing the εtepε of: (a) treating eukaryotic cells in εuch a manner aε to render proteinε, and portionε thereof, preεent in the cellε available for binding to antibodieε specific to the proteins or portions thereof; (b) contacting the product of (a) with an antibody capable of selectively binding to DNA structure εpecific recognition protein, under conditionε appropriate for binding of antibodieε to εelected proteinε or portions thereof for which the antibodies have εpecificity; and (c) detecting binding of the antibody to DNA εtructure εpecific recognition protein. 44. A method of Claim 43 wherein the antibody iε capable of εelectively binding to a eukaryotic DNA εtructure εpecific recognition protein εelected from the group conεisting of: (a) a recombinant protein having DNA structure εpecific recognition activity, encoded by all or at leaεt a region of the nucleotide εequence of SEQ ID No. 6; (b) a recombinant protein having DNA εtructure εpecific recognition activity, encoded by all or at leaεt a region of a nucleotide sequence substantially homologous to the nucleotide sequence of SEQ ID No. 6; (c) a recombinant protein having DNA structure specific recognition activity, encoded by all or at least a region of the nucleotide sequence of SEQ ID No. 8; (d) a recombinant protein having DNA structure εpecific recognition activity, encoded by all or at leaεt a region of a nucleotide εequence εubstantially homologous to the nucleotide εequence of SEQ ID No. 8; (e) a recombinant protein having DNA structure specific recognition activity, encoded by all or at leaεt a region of the nucleotide εequence of SEQ ID No. 9; (f) a recombinant protein having DNA structure specific recognition activity, encoded by all or at least a region of a nucleotide sequence εubεtantially homologous to the nucleotide εequence of SEQ ID No. 9; (g) a recombinant protein having DNA structure εpecific recognition activity, encoded by all or at leaεt a region of the λPtl gene present in E. coli recombinant cells, ATCC Deposit No. 40498; (h) a recombinant protein encoded by DNA having subεtantial homology to all or at leaεt a region of the λPtl gene preεent in E. coli recombinant cells, ATCC Deposit No. 40498; (i) a recombinant protein comprising all or at leaεt a region of the amino acid εequence of SEQ ID No. 7; and (j) a recombinant protein compriεing all or at leaεt a εubstantial portion of the amino acid sequence of the HMG-box domain region of SEQ ID No. 7. 45. A method of Claim 43 wherein the eukaryotic cells are human cells.

Inventors: BROWN STEVEN J, BRUHN SUZANNE L, DONAHUE BRIAN A, ESSIGMANN JOHN M, KELLETT PATTI J, LIPPARD STEPHEN J, PIL PIETER M, TONEY JEFFREY H, BROWN, STEVEN, J., BRUHN, SUZANNE, L., DONAHUE, BRIAN, A., ESSIGMANN, JOHN, M., KELLETT, PATTI, J., LIPPARD, STEPHEN, J., PIL, PIETER, M., TONEY, JEFFREY, H.
Applicants: MASSACHUSETTS INST TECHNOLOGY, MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Application year: 1992
Main classification: C07K13
IPC codes: A61K38, C07K14, C07K16, C12N15, C12P21, C12Q1