bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of the Pairing Gene Ph1 on Centromere Misdivision in Common Wheat
Authors: Vega Juan M , Feldman Moshe 
Published: February 2021

Abstract
The cytologically diploid-like meiotic behavior of hexaploid wheat (i.e., exclusive bivalent pairing of homologues) is largely controlled by the pairing homoeologous gene Ph1. This gene suppresses pairing between homoeologous (partially homologous) chromosomes of the three closely related genomes that compose the hexaploid wheat complement. It has been previously proposed that Ph1 regulates meiotic pairing by determining the pattern of premeiotic arrangement of homologous and homoeologous chromosomes. We therefore assume that Ph1 action may be targeted at the interaction of centromeres with spindle microtubules—an interaction that is critical for movement of chromosomes to their specific interphase positions. Using monosomic lines of common wheat, we studied the effect of this gene on types and rates of centromere division of univalents at meiosis. In the presence of the normal two doses of Ph1, the frequency of transverse breakage (misdivision) of the centromere of univalent chromosomes was high in both first and second meiotic divisions; whereas with zero dose of the gene, this frequency was drastically reduced. The results suggest that Ph1 is a trans-acting gene affecting centromere-microtubules interaction. The findings are discussed in the context of the effect of Ph1 on interphase chromosome arrangement.
Suppressors of an Arabidopsis thaliana phyB Mutation Identify Genes That Control Light Signaling and Hypocotyl Elongation
Authors: Reed Jason W , Elumalai Rangasamy P , Chory Joanne 
Published: February 2021

Abstract
Ambient light controls the development and physiology of plants. The Arabidopsis thaliana photoreceptor phytochrome B (PHYB) regulates developmental light responses at both seedling and adult stages. To identify genes that mediate control of development by light, we screened for suppressors of the long hypocotyl phenotype caused by a phyB mutation. Genetic analyses show that the shy (short hypocotyl) mutations we have isolated fall in several loci. Phenotypes of the mutants suggest that some of the genes identified have functions in control of light responses. Other loci specifically affect cell elongation or expansion.
Selection with Recurrent Backcrossing to Develop Congenic Lines for Quantitative Trait Loci Analysis
Authors: Hill William G 
Published: February 2021

Abstract
Sewall Wright suggested that genes of large effect on a quantitative trait could be isolated by recurrent backcrossing with selection on the trait. Loci [quantitative trait loci (QTL)] at which the recurrent and nonrecurrent lines have genes of different large effect on the trait would remain segregating, while other loci would become fixed for the gene carried by the recurrent parent. If the recurrent line is inbred and the backcrossing and selection is conducted in a series of replicate lines, in each of which only one backcross parent is selected for each generation, the lines will become congenic to the recurrent parent except for the QTL of large effect and closely linked regions of the genome, and these regions can be identified using a dense set of markers that differ between the parental lines. Such lines would be particularly valuable for subsequent fine-scale mapping and gene cloning; but by chance, even QTL of large effect will be lost from some lines. The probability that QTL of specified effect remain segregating is computed as a function of its effect on the trait, the intensity of selection, and the number of generations of backcrossing. Analytical formulas are given for one or two loci, and simulation is used for more. It is shown that the method could have substantial discriminating ability and thus potential practical value.
Factors Affecting Inverted Repeat Stimulation of Recombination and Deletion in Saccharomyces cerevisiae
Authors: Lobachev Kirill S , Shor Boris M , Tran Hiep T , Taylor Wendy , Keen J Dianne , Resnick Michael A , Gordenin Dmitry A 
Published: February 2021

Abstract
Inverted DNA repeats are an at-risk motif for genetic instability that can induce both deletions and recombination in yeast. We investigated the role of the length of inverted repeats and size of the DNA separating the repeats for deletion and recombination. Stimulation of both deletion and recombination was directly related to the size of inverted repeats and inversely related to the size of intervening spacers. A perfect palindrome, formed by two 1.0-kb URA3-inverted repeats, increased intra- and interchromosomal recombination in the adjacent region 2,400-fold and 17,000-fold, respectively. The presence of a strong origin of replication in the spacer reduced both rates of deletion and recombination. These results support a model in which the stimulation of deletion and recombination by inverted repeats is initiated by a secondary structure formed between single-stranded DNA of inverted repeats during replication.
Antimutator Mutants in Bacteriophage T4 and Escherichia coli
Authors: Schaaper Roel M 
Published: February 2021

Abstract
Antimutators are mutant strains that have reduced mutation rates compared to the corresponding wild-type strain. Their existence, along with mutator mutants that have higher mutation rates compared to the wild-type strain, are powerful evidence that mutation rates are genetically controlled. Compared to mutator mutants, antimutators have a very distinguishing property. Because they prevent normally occurring mutations, they, uniquely, are capable of providing insight into the mechanisms of spontaneous mutations. In this review, antimutator mutants are discussed in bacteriophage T4 and the bacterium Escherichia coli, with regard to their properties, possible mechanisms, and implications for the sources of spontaneous mutations in these two organisms.
Hypermutability in Carcinogenesis
Authors: Strauss Bernard S 
Published: February 2021

AbstractThe presence of numerous chromosomal changes and point mutations in tumors is well established. At least some of these changes play a role in the development of the tumors. It has been suggested that the number of these genetic changes requires that tumorigenesis involves an increase in mutation rate. However, the presence of numerous changes can also be accounted for by efficient selection. What is required to settle the issue is some measure of nonselected mutations in tumors. In order to determine whether the tumor suppressor TP53 (coding for the protein p53) is hypermutable at some stage of carcinogenesis, the frequency of silent and multiple mutations in this gene has been examined. Silent mutations make up ~3% of the total recorded but constitute 9.5% of the mutations found in tumors with multiple mutations. Multiple closely linked mutations are also observed. Such multiple mutations suggest the operation of an error-prone replication process in a subclass of cells. The published data indicate that TP53 is hypermutable at some stage of tumor development. It is not yet clear whether TP53 is unique or whether other genes display a similar pattern of silent and multiple mutations.
Functional Overlap in Mismatch Repair by Human MSH3 and MSH6
Authors: Umar Asad , Risinger John I , Glaab Warren E , Tindall Kenneth R , Barrett J Carl , Kunkel Thomas A 
Published: February 2021

Abstract
Three human genes, hMSH2, hMSH3, and hMSH6, are homologues of the bacterial MutS gene whose products bind DNA mismatches to initiate strand-specific repair of DNA replication errors. Several studies suggest that a complex of hMSH2·hMSH6 (hMutSα) functions primarily in repair of base·base mismatches or single extra bases, whereas a hMSH2·hMSH3 complex (hMutSβ) functions chiefly in repair of heteroduplexes containing two to four extra bases. In the present study, we compare results with a tumor cell line (HHUA) that is mutant in both hMSH3 and hMSH6 to results with derivative clones containing either wild-type hMSH3 or wild-type hMSH6, introduced by microcell-mediated transfer of chromosome 5 or 2, respectively. HHUA cells exhibit marked instability at 12 different microsatellite loci composed of repeat units of 1 to 4 base pairs. Compared to normal cells, HHUA cells have mutation rates at the HPRT locus that are elevated 500-fold for base substitutions and 2400-fold for single-base frameshifts. Extracts of HHUA cells are defective in strand-specific repair of substrates containing base·base mismatches or 1–4 extra bases. Transfer of either chromosome 5 (hMSH3) or 2 (hMSH6) into HHUA cells partially corrects instability at the microsatellite loci and also the substitution and frameshift mutator phenotypes at the HPRT locus. Extracts of these lines can repair some, but not all, heteroduplexes. The combined mutation rate and mismatch repair specificity data suggest that both hMSH3 and hMSH6 can independently participate in repair of replication errors containing base·base mismatches or 1–4 extra bases. Thus, these two gene products share redundant roles in controlling mutation rates in human cells.
Posttranslational Inhibition of Ty1 Retrotransposition by Nucleotide Excision Repair/Transcription Factor TFIIH Subunits Ssl2p and Rad3p
Authors: Lee Bum-Soo , Lichtenstein Conrad P , Faiola Brenda , Rinckel Lori A , Wysock William , Curcio M Joan , Garfinkel David J 
Published: February 2021

Abstract
rtt4-1 (regulator of Ty transposition) is a cellular mutation that permits a high level of spontaneous Ty1 retrotransposition in Saccharomyces cerevisiae. The RTT4 gene is allelic with SSL2 (RAD25), which encodes a DNA helicase present in basal transcription (TFIIH) and nucleotide excision repair (NER) complexes. The ssl2-rtt (rtt4-1) mutation stimulates Ty1 retrotransposition, but does not alter Ty1 target site preferences, or increase cDNA or mitotic recombination. In addition to ssl2-rtt, the ssl2-dead and SSL2-1 mutations stimulate Ty1 transposition without altering the level of Ty1 RNA or proteins. However, the level of Ty1 cDNA markedly increases in the ssl2 mutants. Like SSL2, certain mutations in another NER/TFIIH DNA helicase encoded by RAD3 stimulate Ty1 transposition. Although Ssl2p and Rad3p are required for NER, inhibition of Ty1 transposition is independent of Ssl2p and Rad3p NER functions. Our work suggests that NER/TFIIH subunits antagonize Ty1 transposition posttranslationally by inhibiting reverse transcription or destabilizing Ty1 cDNA.
High Frequency Recombination During the Sexual Cycle of Dictyostelium discoideum
Authors: Francis David 
Published: February 2021

Abstract
Analysis of Dictyostelium development and cell biology has suffered from the lack of an ordinary genetic system whereby genes can be arranged in new combinations. Genetic exchange between two long ignored strains, A2Cycr and WS205 is here reexamined. Alleles which differ in size or restriction sites between these two strains were found for seven genes. Six of these are in two clusters on chromosome 2. Frequencies of recombinant progeny indicate that the genetic map of the two mating strains is colinear with the physical map recently worked out for the standard nonsexual strain, NC4. The rate of recombination is high, about 0.1% per kilobase in three different regions of chromosome 2. This value is comparable to rates found in yeast, and will permit fine dissection of the genome.
Second-Site Noncomplementation Identifies Genomic Regions Required for Drosophila Nonmuscle Myosin Function During Morphogenesis
Authors: Halsell Susan R , Kiehart Daniel P 
Published: February 2021

Abstract
Drosophila is an ideal metazoan model system for analyzing the role of nonmuscle myosin-II (henceforth, myosin) during development. In Drosophila, myosin function is required for cytokinesis and morphogenesis driven by cell migration and/or cell shape changes during oogenesis, embryogenesis, larval development and pupal metamorphosis. The mechanisms that regulate myosin function and the supramolecular structures into which myosin incorporates have not been systematically characterized. The genetic screens described here identify genomic regions that uncover loci that facilitate myosin function. The nonmuscle myosin heavy chain is encoded by a single locus, zipper. Contiguous chromosomal deficiencies that represent approximately 70% of the euchromatic genome were screened for genetic interactions with two recessive lethal alleles of zipper in a second-site noncomplementation assay for the malformed phenotype. Malformation in the adult leg reflects aberrations in cell shape changes driven by myosin-based contraction during leg morphogenesis. Of the 158 deficiencies tested, 47 behaved as second-site noncomplementors of zipper. Two of the deficiencies are strong interactors, 17 are intermediate and 28 are weak. Finer genetic mapping reveals that mutations in cytoplasmic tropomyosin and viking (collagen IV) behave as second-site noncomplementors of zipper during leg morphogenesis and that zipper function requires a previously uncharacterized locus, E3.10/J3.8, for leg morphogenesis and viability.
Evidence for a Multistep Control in Transposition of I Factor in Drosophila melanogaster
Authors: de La Roche Saint André Christophe , Bregliano Jean-Claude 
Published: February 2021

Abstract
Drosophila melanogaster strains belong to one of two interactive categories, inducer (I) or reactive (R), with respect to the I-R system of hybrid dysgenesis. The dysgenic interaction results from the presence of several transposition-competent copies of a LINE-like element, the I factor, only in the genome of I strains. When a cross is performed between I males and R females, I factor transposes at high frequency in the germ line of F1 daughters, known as SF females. This transposition burst results in the sterility of SF females. I factor transposes by reverse transcription of a full-length transcript. Specific RT-PCR experiments were done to compare the amount of I factor transcript in samples corresponding to various transposition frequencies. The sensitivity of the method allowed the ready detection of the I factor RNA in every tissue and genetic background examined. Comparison of amplification signals suggests that I factor activity in ovaries is regulated at different levels. First, the amount of I factor RNA subjected to negative and positive regulation. Whereas the negative control, which limits transposition in nonpermissive contexts, may be exerted by an I factor encoded repressor function, the positive control is linked to reactivity level, a cellular state maternally inherited from R mothers. Additionally, negative regulation is also exerted downstream of I factor RNA. This differs notably from previous conclusions in which transcription was envisaged as the main level of regulation of the I factor transposition.
Heteroplasmy, Length and Sequence Variation in the mtDNA Control Regions of Three Percid Fish Species (Perca fluviatilis, Acerina cernua, Stizostedion lucioperca)
Authors: Nesbø Camilla Lothe , Arab Mohammed O , Jakobsen Kjetill S 
Published: February 2021

Abstract
The nucleotide sequence of the control region and flanking tRNA genes of perch (Perca fluviatilis) mtDNA was determined. The organization of this region is similar to that of other vertebrates. A tandem array of 10-bp repeats, associated with length variation and heteroplasmy was observed in the 5′ end. While the location of the array corresponds to that reported in other species, the length of the repeated unit is shorter than previously observed for tandem repeats in this region. The repeated sequence was highly similar to the Mt5 element which has been shown to specifically bind a putative D-loop DNA termination protein. Of 149 perch analyzed, 74% showed length variation heteroplasmy. Single-cell PCR on oocytes suggested that the high level of heteroplasmy is passively maintained by maternal transmission. The array was also observed in the two other percid species, ruffe (Acerina cernua) and zander (Stizostedion lucioperca). The array and the associated length variation heteroplasmy are therefore likely to be general features of percid mtDNAs. Among the perch repeats, the mutation pattern is consistent with unidirectional slippage, and statistical analyses supported the notion that the various haplotypes are associated with different levels of heteroplasmy. The variation in array length among and within species is ascribed to differences in predicted stability of secondary structures made between repeat units.
Molecular Genetic Dissection of Mouse Unconventional Myosin-VA: Tail Region Mutations
Authors: Huang Jian-Dong , Mermall Valerie , Strobel Marjorie C , Russell Liane B , Mooseker Mark S , Copeland Neal G , Jenkins Nancy A 
Published: February 2021

Abstract
We used an RT-PCR-based sequencing approach to identify the mutations responsible for 17 viable dilute alleles, a mouse-coat-color locus encoding unconventional myosin-VA. Ten of the mutations mapped to the MyoVA tail and are reported here. These mutations represent the first extensive collection of tail mutations reported for any unconventional mammalian myosin. They identify sequences important for tail function and identify domains potentially involved in cargo binding and/or proper folding of the MyoVA tail. Our results also provide support for the notion that different myosin tail isoforms produced by alternative splicing encode important cell-type-specific functions.
Genetic Identification of Multiple Loci That Control Breast Cancer Susceptibility in the Rat
Authors: Shepel Laurie A , Lan Hong , Haag Jill D , Brasic Gerlyn M , Gheen Megan E , Simon Jason S , Hoff Peter , Newton Michael A , Gould Michael N 
Published: February 2021

Abstract
We have used a rat model of induced mammary carcinomas in an effort to identify breast cancer susceptibility genes. Using genetic crosses between the carcinoma-resistant Copenhagen (COP) and carcinoma-sensitive Wistar-Furth rats, we have confirmed the identification of the Mcs1 locus that modulates tumor number. We have now also identified two additional loci, Mcs2 and Mcs3. These three loci map to chromosomes 2, 7, and 1, respectively, and interact additively to suppress mammary carcinoma development in the COP strain. They are responsible for a major portion of the tumor-resistant phenotype of the COP rat. No loss of heterozygosity was observed surrounding the three loci. A fourth COP locus, Mcs4, has also been identified on chromosome 8 and acts in contrast to increase the number of carcinomas. These results show that mammary carcinoma susceptibility in the COP rat is a polygenic trait. Interestingly, a polymorphism in the human genomic region homologous to the rat Mcs4 region is associated with an increased breast cancer risk in African-American women. The isolation of the Mcs genes may help elucidate novel mechanisms of carcinogenesis, provide information important for human breast cancer risk estimation, and also provide unique drug discovery targets for breast cancer prevention.
Molecular Mapping of Segregation Distortion Loci in Aegilops tauschii
Authors: Faris J D , Laddomada B , Gill B S 
Published: February 2021

Abstract
Distorted segregation ratios of genetic markers are often observed in progeny of inter- and intraspecific hybrids and may result from competition among gametes or from abortion of the gamete or zygote. In this study, 194 markers mapped in an Aegilops tauschii F2 population were surveyed for distorted segregation ratios. Region(s) with skewed segregation ratios were detected on chromosomes 1D, 3D, 4D, and 7D. These distorter loci are designated as QSd.ksu-1D, QSd.ksu-3D, QSd.ksu-4D, and QSd.ksu-7D. Three regions of segregation distortion identified on chromosome 5D were analyzed in two sets of reciprocal backcross populations to analyze the effect of sex and cytoplasm on segregation distortion. Extreme distortion of marker segregation ratios was observed in populations in which the F1 was used as the male parent, and ratios were skewed in favor of TA1691 alleles. There was some evidence of differential transmission caused by nucleo-cytoplasmic interactions. Our results agree with other studies stating that loci affecting gametophyte competition in male gametes are located on 5DL. The distorter loci on 5DL are designated as QSd.ksu-5D.1, QSd.ksu-5D.2, and QSd.ksu-5D.3.
Plastome Mutator–Induced Alterations Arise in Oenothera Chloroplast DNA Through Template Slippage
Authors: Stoike Lara L , Sears Barbara B 
Published: February 2021

Abstract
The plastome mutator of Oenothera hookeri strain Johansen causes deletions and duplications at target sites defined by direct repeats in the plastid genome. Previous studies characterized the mutations long after they had occurred and could not discriminate between the possibilities that the plastome mutator acted through unequal homologous recombination or template slippage. From the known hotspots, the rRNA spacer in the large inverted repeat was chosen for this study because it contains both direct and indirect repeats. Identical deletions were recovered from independently derived plants; the altered regions were always flanked by direct repeats. The regions in which the deletions occurred have the potential to form secondary structures that would stabilize the intervening sequence. Of the two affected regions, the one with the stronger potential secondary structure was altered more frequently. Because no duplication products or inversions were recovered, it is proposed that the plastome mutator acts through template slippage rather than through a recombination mechanism.
Mutations Synthetically Lethal with cep1 Target S. cerevisiae Kinetochore Components
Authors: Baker Richard E , Harris Kendra , Zhang Keming 
Published: February 2021

Abstract
CP1 (encoded by CEP1) is a Saccharomyces cerevisiae chromatin protein that binds a DNA element conserved in centromeres and in the 5′-flanking DNA of methionine biosynthetic (MET) genes. Strains lacking CP1 are defective in chromosome segregation and MET gene transcription, leading to the hypothesis that CP1 plays a general role in assembling higher order chromatin structures at genomic sites where it is bound. A screen for mutations synthetically lethal with a cep1 null allele yielded five recessive csl (cep1 synthetic lethal) mutations, each defining a unique complementation group. Four of the five mutations synergistically increased the loss rate of marker chromosomes carrying a centromere lacking the CP1 binding site, suggesting that the cep1 synthetic lethality was due to chromosome segregation defects. Three of these four CSL genes were subsequently found to be known or imputed kinetochore genes: CEP3, NDC10, and CSE4. The fourth, CSL4, corresponded to ORF YNL232w on chromosome XIV, and was found to be essential. A human cDNA was identified that encoded a protein homologous to Csl4 and that complemented the csl4-1 mutation. The results are consistent with the view that the major cellular role of CP1 is to safeguard the biochemical integrity of the kinetochore.