7178 Nucleic Acids Research, 2011, Vol. 39, No. 16 24. Siddiqui-Jain,A., Grand,C.L., Bearss,D.J. and Hurley,L.H. (2002) Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription. Proc. Natl Acad. Sci. USA, 99, 11593–11598. 25. Qin,Y., Rezler,E.M., Gokhale,V., Sun,D. and Hurley,L.H. (2007) Characterization of the G-quadruplexes in the duplex nuclease hypersensitive element of the PDGF-A promoter and modulation of PDGF-A promoter activity by TMPyP4. Nucleic Acids Res., 35, 7698–7713. 26. Guo,K., Pourpak,A., Beetz-Rogers,K., Gokhale,V., Sun,D. and Hurley,L.H. (2007) Formation of pseudosymmetrical G-quadruplex and i-motif structures in the proximal promoter region of the RET oncogene. J. Am. Chem. Soc., 129, 10220–10228. 27. Connor,A.C., Frederick,K.A., Morgan,E.J. and McGown,L.B. (2006) Insulin capture by an insulin-linked polymorphic region G-quadruplex DNA oligonucleotide. J. Am. Chem. Soc., 128, 4986–4991. 28. Lew,A., Rutter,W.J. and Kennedy,G.C. (2000) Unusual DNA structure of the diabetes susceptibility locus IDDM2 and its effect on transcription by the insulin promoter factor Pur-1/MAZ. Proc. Natl Acad. Sci. USA, 97, 12508–12512. 29. Arora,A., Dutkiewicz,M., Scaria,V., Hariharan,M., Maiti,S. and Kurreck,J. (2008) Inhibition of translation in living eukaryotic cells by an RNA G-quadruplex motif. RNA, 14, 1290–1296. 30. Kumari,S., Bugaut,A., Huppert,J.L. and Balasubramanian,S. (2007) An RNA G-quadruplex in the 50 UTR of the NRAS proto-oncogene modulates translation. Nat. Chem. Biol., 3, 218–221. 31. Eddy,J. and Maizels,N. (2008) Conserved elements with potential to form polymorphic G-quadruplex structures in the ﬁrst intron of human genes. Nucleic Acids Res., 36, 1321–1333. 32. Kikin,O., D’Antonio,L. and Bagga,P.S. (2006) QGRS Mapper: a web-based server for predicting G-quadruplexes in nucleotide sequences. Nucleic Acids Res., 34, W676–W682. 33. Harrington,C., Lan,Y. and Akman,S.A. (1997) The identiﬁcation and characterization of a G4-DNA resolvase activity. J. Biol. Chem., 272, 24631–24636. 34. Sun,H., Karow,J.K., Hickson,I.D. and Maizels,N. (1998) The Bloom’s syndrome helicase unwinds G4 DNA. J. Biol. Chem., 273, 27587–27592. 35. Wu,Y., Shin-Ya,K. and Brosh,R.M. Jr (2008) FANCJ helicase defective in Fanconia anemia and breast canceruUnwinds G-quadruplex DNA to defend genomic atability. Mol. Cell. Biol., 28, 4116–4128. 36. Vaughn,J.P., Creacy,S.D., Routh,E.D., Joyner-Butt,C., Jenkins,G.S., Pauli,S., Nagamine,Y. and Akman,S.A. (2005) The DEXH protein product of the DHX36 gene is the major source of tetramolecular quadruplex G4-DNA resolving activity in HeLa cell lysates. J. Biol. Chem., 280, 38117–38120. 37. Creacy,S.D., Routh,E.D., Iwamoto,F., Nagamine,Y., Akman,S.A. and Vaughn,J.P. (2008) G4 Resolvase 1 binds both DNA and RNA tetramolecular quadruplex with high afﬁnity and is the major source of tetramolecular quadruplex G4-DNA and G4-RNA resolving activity in HeLa cells. J. Biol. Chem., 283, 34626–34634. 38. Lattmann,S., Giri,B., Vaughn,J.P., Akman,S.A. and Nagamine,Y. (2010) Role of the amino terminal RSM domain in the recognition and resolution of guanine quadruplex RNA by the DEAH-box RNA helicase RHAU. Nucleic Acids Res., 38, 6219–6233. 39. Maxam,A. and Gilbert,W. (1980) Sequencing end-labeled DNA with base-speciﬁc chemical cleavages. Meth. Enzymol., 65, 499–560. 40. Tran,H., Schilling,M., Wirbelauer,C., Hess,D. and Nagamine,Y. (2004) Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU. Mol. Cell, 13, 101–111. 41. Giraldo,R., Suzuki,M., Chapman,L. and Rhodes,D. (1994) Promotion of parallel DNA quadruplexes by a yeast telomere binding protein: a circular dichroism study. Proc. Natl Acad. Sci. USA, 91, 7658–7662. 42. Paramasivan,S., Rujan,I. and Bolton,P.H. (2007) Circular dichroism of quadruplex DNAs: applications to structure, cation effects and ligand binding. Methods, 43, 324–331. 43. Bardin,C. and Leroy,J.L. (2008) The formation pathway of tetramolecular G-quadruplexes. Nucleic Acids Res., 36, 477–488. 44. Hud,N.V., Smith,F.W., Anet,F.A. and Feigon,J. (1996) The selectivity for K+ versus Na+ in DNA quadruplexes is dominated by relative free energies of hydration: a thermodynamic analysis by 1 H NMR. Biochemistry, 35, 15383–15390. 45. Datta,B. and Armitage,B.A. (2001) Hybridization of PNA to structured DNA targets: quadruplex invasion and the overhang effect. J. Am. Chem. Soc., 123, 9612–9619. 46. Green,J.J., Ying,L., Klenerman,D. and Balasubramanian,S. (2003) Kinetics of unfolding the human telomeric DNA quadruplex using a PNA trap. J. Am. Chem. Soc., 125, 3763–3767. 47. Bashkirov,V.I., Scherthan,H., Solinger,J.A., Buerstedde,J.M. and Heyer,W.D. (1997) A mouse cytoplasmic exoribonuclease (mXRN1p) with preference for G4 tetraplex substrates. J. Cell Biol., 136, 761–773. 48. Boder,E.T., Midelfort,K.S. and Wittrup,K.D. (2000) Directed evolution of antibody fragments with monovalent femtomolar antigen-binding afﬁnity. Proc. Natl Acad. Sci. USA, 97, 10701–10705. 49. Kankia,B.I., Barany,G. and Musier-Forsyth,K. (2005) Unfolding of DNA quadruplexes induced by HIV-1 nucleocapsid protein. Nucleic Acids Res., 33, 4395–4403. 50. Torigoe,H. and Furukawa,A. (2007) Tetraplex structure of ﬁssion yeast telomeric DNA and unfolding of the tetraplex on the interaction with telomeric DNA binding protein Pot1. J. Biochem., 141, 57–68. 51. Paramasivam,M., Membrino,A., Cogoi,S., Fukuda,H., Nakagama,H. and Xodo,L.E. (2009) Protein hnRNP A1 and its derivative Up1 unfold quadruplex DNA in the human KRAS promoter: implications for transcription. Nucleic Acids Res., 37, 2841–2853. 52. Fan,J.-H., Bochkareva,E., Bochkarev,A. and Gray,D.M. (2009) Circular dichroism spectra and electrophoretic mobility shift assays show that human replication protein A binds and melts intramolecular G-quadruplex structures. Biochemistry, 48, 1099–1111. 53. Liu,J.-Q., Chen,C.-Y., Xue,Y., Hao,Y.-H. and Zheng,T. (2010) G-quadruplex hinders translocation of BLM helicase on DNA: a real-time ﬂuorescence spectroscopic unwinding study and comparison with duplex substrates. J. Am. Chem. Soc., 132, 10521–10527. 54. Plyler,J., Jasheway,K., Tuesuwan,B., Karr,J., Brennan,J.S., Kerwin,S.M. and David,W.M. (2009) Real-time investigation of SV40 large T-antigen helicase activity using surface plasmon resonance. Cell Biochem. Biophys., 53, 43–52. 55. Huber,M.D., Lee,D.C. and Maizels,N. (2002) G4 DNA unwinding by BLM and Sgs1p: substrate speciﬁcity and substrate-speciﬁc inhibition. Nucleic Acids Res., 30, 3954–3961. 56. Zhang,S. and Grosse,F. (2004) Multiple functions of nuclear DNA helicase II (RNA helicase A) in nucleic acid metabolism. Acta Biochim. Biophys., 36, 177–183. 57. Chalupnı´ kov a´,K., Lattmann,S., Selak,N., Iwamoto,F., Fujiki,Y. and Nagamine,Y. (2008) Recruitment of the RNA Helicase RHAU to Stress Granules via a Unique RNA-binding Domain. J. Biol. Chem., 283, 35186–35198. 58. Iwamoto,F., Stadler,M., Chalupnikova,K., Oakeley,E. and Nagamine,Y. (2008) Transcription-dependent nucleolar cap localization and possible nuclear function of DExH RNA helicase RHAU. Exp. Cell Res., 314, 1378–1391.