Roles of DNA Helicases in the Mediation and Regulation of Homologous Recombination

  • James M. Daley
  • Hengyao Niu
  • Patrick SungEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 973)


Homologous recombination (HR) is an evolutionarily conserved process that eliminates DNA double-strand breaks from chromosomes, repairs injured DNA replication forks, and helps orchestrate meiotic chromosome segregation. Recent studies have shown that DNA helicases play multifaceted roles in HR mediation and regulation. In particular, the S. cerevisiae Sgs1 helicase and its human ortholog BLM helicase are involved in not only the resection of the primary lesion to generate single-stranded DNA to prompt the assembly of the HR machinery, but they also function in somatic cells to suppress the formation of chromosome arm crossovers during HR. On the other hand, the S. cerevisiae Mph1 and Srs2 helicases, and their respective functional equivalents in other eukaryotes, suppress spurious HR events and favor the formation of noncrossovers via distinct mechanisms. Thus, the functional integrity of the HR process and HR outcomes are dependent upon these helicase enzymes. Since mutations in some of these helicases lead to cancer predisposition in humans and mice, studies on them have clear relevance to human health and disease.


Homologous Recombination Fanconi Anemia Replication Fork Helicase Activity Holliday Junction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Lieber MR. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem. 2010;79:181–211.PubMedCrossRefGoogle Scholar
  2. 2.
    Mimitou EP, Symington LS. Nucleases and helicases take center stage in homologous recombination. Trends Biochem Sci. 2009;34:264–72.PubMedCrossRefGoogle Scholar
  3. 3.
    San Filippo J, Sung P, Klein H. Mechanism of eukaryotic homologous recombination. Annu Rev Biochem. 2008;77:229–57.PubMedCrossRefGoogle Scholar
  4. 4.
    Gravel S, Chapman JR, Magill C, Jackson SP. DNA helicases Sgs1 and BLM promote DNA double-strand break resection. Genes Dev. 2008;22:2767–72.PubMedCrossRefGoogle Scholar
  5. 5.
    Mimitou EP, Symington LS. Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing. Nature. 2008;455:770–4.PubMedCrossRefGoogle Scholar
  6. 6.
    Zhu Z, Chung WH, Shim EY, Lee SE, Ira G. Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends. Cell. 2008;134:981–94.PubMedCrossRefGoogle Scholar
  7. 7.
    Schwartz EK, Heyer WD. Processing of joint molecule intermediates by structure-selective endonucleases during homologous recombination in eukaryotes. Chromosoma. 2011;120:109–27.PubMedCrossRefGoogle Scholar
  8. 8.
    Hanada K, Ukita T, Kohno Y, Saito K, Kato J, Ikeda H. RecQ DNA helicase is a suppressor of illegitimate recombination in Escherichia coli. Proc Natl Acad Sci USA. 1997;94:3860–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Gangloff S, McDonald JP, Bendixen C, Arthur L, Rothstein R. The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. Mol Cell Biol. 1994;14:8391–8.PubMedGoogle Scholar
  10. 10.
    Chang M, Bellaoui M, Zhang C, Desai R, Morozov P, Delgado-Cruzata L, Rothstein R, Freyer GA, Boone C, Brown GW. RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex. EMBO J. 2005;24:2024–33.PubMedCrossRefGoogle Scholar
  11. 11.
    Mullen JR, Nallaseth FS, Lan YQ, Slagle CE, Brill SJ. Yeast Rmi1/Nce4 controls genome stability as a subunit of the Sgs1-Top3 complex. Mol Cell Biol. 2005;25:4476–87.PubMedCrossRefGoogle Scholar
  12. 12.
    Ii M, Brill SJ. Roles of SGS1, MUS81, and RAD51 in the repair of lagging-strand replication defects in Saccharomyces cerevisiae. Curr Genet. 2005;48:213–25.PubMedCrossRefGoogle Scholar
  13. 13.
    Onoda F, Seki M, Miyajima A, Enomoto T. Elevation of sister chromatid exchange in Saccharomyces cerevisiae sgs1 disruptants and the relevance of the disruptants as a system to evaluate mutations in Bloom’s syndrome gene. Mutat Res. 2000;459:203–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Gangloff S, Soustelle C, Fabre F. Homologous recombination is responsible for cell death in the absence of the Sgs1 and Srs2 helicases. Nat Genet. 2000;25:192–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Ira G, Malkova A, Liberi G, Foiani M, Haber JE. Srs2 and Sgs1-Top3 suppress crossovers during double-strand break repair in yeast. Cell. 2003;115:401–11.PubMedCrossRefGoogle Scholar
  16. 16.
    Wu L, Hickson ID. The Bloom’s syndrome helicase suppresses crossing over during homologous recombination. Nature. 2003;426:870–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Sugawara N, Haber JE. Repair of DNA double strand breaks: in vivo biochemistry. Methods Enzymol. 2006;408:416–29.PubMedCrossRefGoogle Scholar
  18. 18.
    Krogh BO, Symington LS. Recombination proteins in yeast. Annu Rev Genet. 2004;38:233–71.PubMedCrossRefGoogle Scholar
  19. 19.
    Bae SH, Seo YS. Characterization of the enzymatic properties of the yeast dna2 Helicase/endonuclease suggests a new model for Okazaki fragment processing. J Biol Chem. 2000;275:38022–31.PubMedCrossRefGoogle Scholar
  20. 20.
    Budd ME, Choe WC, Campbell JL. DNA2 encodes a DNA helicase essential for replication of eukaryotic chromosomes. J Biol Chem. 1995;270:26766–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Cejka P, Cannavo E, Polaczek P, Masuda-Sasa T, Pokharel S, Campbell JL, Kowalczykowski SC. DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11-Rad50-Xrs2. Nature. 2010;467:112–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Niu H, Chung WH, Zhu Z, Kwon Y, Zhao W, Chi P, Prakash R, Seong C, Liu D, Lu L, et al. Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae. Nature. 2010;467:108–11.PubMedCrossRefGoogle Scholar
  23. 23.
    Chu WK, Hickson ID. RecQ helicases: multifunctional genome caretakers. Nat Rev Cancer. 2009;9:644–54.PubMedCrossRefGoogle Scholar
  24. 24.
    Cejka P, Kowalczykowski SC. The full-length Saccharomyces cerevisiae Sgs1 protein is a vigorous DNA helicase that preferentially unwinds holliday junctions. J Biol Chem. 2010;285:8290–301.PubMedCrossRefGoogle Scholar
  25. 25.
    Raynard S, Bussen W, Sung P. A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIalpha, and BLAP75. J Biol Chem. 2006;281:13861–4.PubMedCrossRefGoogle Scholar
  26. 26.
    Singh TR, Ali AM, Busygina V, Raynard S, Fan Q, Du CH, Andreassen PR, Sung P, Meetei AR. BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome. Genes Dev. 2008;22:2856–68.PubMedCrossRefGoogle Scholar
  27. 27.
    Wu L, Bachrati CZ, Ou J, Xu C, Yin J, Chang M, Wang W, Li L, Brown GW, Hickson ID. BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. Proc Natl Acad Sci USA. 2006;103:4068–73.PubMedCrossRefGoogle Scholar
  28. 28.
    Borner GV, Kleckner N, Hunter N. Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell. 2004;117:29–45.PubMedCrossRefGoogle Scholar
  29. 29.
    Jessop L, Rockmill B, Roeder GS, Lichten M. Meiotic chromosome synapsis-promoting proteins antagonize the anti-crossover activity of sgs1. PLoS Genet. 2006;2:e155.PubMedCrossRefGoogle Scholar
  30. 30.
    Oh SD, Lao JP, Hwang PY, Taylor AF, Smith GR, Hunter N. BLM ortholog, Sgs1, prevents aberrant crossing-over by suppressing formation of multichromatid joint molecules. Cell. 2007;130:259–72.PubMedCrossRefGoogle Scholar
  31. 31.
    Evans E, Sugawara N, Haber JE, Alani E. The Saccharomyces cerevisiae Msh2 mismatch repair protein localizes to recombination intermediates in vivo. Mol Cell. 2000;5:789–99.PubMedCrossRefGoogle Scholar
  32. 32.
    Sugawara N, Goldfarb T, Studamire B, Alani E, Haber JE. Heteroduplex rejection during single-strand annealing requires Sgs1 helicase and mismatch repair proteins Msh2 and Msh6 but not Pms1. Proc Natl Acad Sci USA. 2004;101:9315–20.PubMedCrossRefGoogle Scholar
  33. 33.
    Tay YD, Sidebotham JM, Wu L. Mph1 requires mismatch repair-independent and -dependent functions of MutSalpha to regulate crossover formation during homologous recombination repair. Nucleic Acids Res. 2010;38:1889–901.PubMedCrossRefGoogle Scholar
  34. 34.
    German J, Sanz MM, Ciocci S, Ye TZ, Ellis NA. Syndrome-causing mutations of the BLM gene in persons in the Bloom’s Syndrome Registry. Hum Mutat. 2007;28:743–53.PubMedCrossRefGoogle Scholar
  35. 35.
    Chaganti RS, Schonberg S, German J. A manyfold increase in sister chromatid exchanges in Bloom’s syndrome lymphocytes. Proc Natl Acad Sci USA. 1974;71:4508–12.PubMedCrossRefGoogle Scholar
  36. 36.
    Chester N, Kuo F, Kozak C, O’Hara CD, Leder P. Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom’s syndrome gene. Genes Dev. 1998;12:3382–93.PubMedCrossRefGoogle Scholar
  37. 37.
    Goss KH, Risinger MA, Kordich JJ, Sanz MM, Straughen JE, Slovek LE, Capobianco AJ, German J, Boivin GP, Groden J. Enhanced tumor formation in mice heterozygous for Blm mutation. Science. 2002;297:2051–3.PubMedCrossRefGoogle Scholar
  38. 38.
    Bachrati CZ, Borts RH, Hickson ID. Mobile D-loops are a preferred substrate for the Bloom’s syndrome helicase. Nucleic Acids Res. 2006;34:2269–79.PubMedCrossRefGoogle Scholar
  39. 39.
    Mohaghegh P, Karow JK, Brosh Jr RM, Bohr VA, Hickson ID. The Bloom’s and Werner’s syndrome proteins are DNA structure-specific helicases. Nucleic Acids Res. 2001;29:2843–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Orren DK, Theodore S, Machwe A. The Werner syndrome helicase/exonuclease (WRN) disrupts and degrades D-loops in vitro. Biochemistry. 2002;41:13483–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Popuri V, Bachrati CZ, Muzzolini L, Mosedale G, Costantini S, Giacomini E, Hickson ID, Vindigni A. The Human RecQ helicases, BLM and RECQ1, display distinct DNA substrate specificities. J Biol Chem. 2008;283:17766–76.PubMedCrossRefGoogle Scholar
  42. 42.
    Sharma S, Sommers JA, Choudhary S, Faulkner JK, Cui S, Andreoli L, Muzzolini L, Vindigni A, Brosh Jr RM. Biochemical analysis of the DNA unwinding and strand annealing activities catalyzed by human RECQ1. J Biol Chem. 2005;280:28072–84.PubMedCrossRefGoogle Scholar
  43. 43.
    Sun H, Karow JK, Hickson ID, Maizels N. The Bloom’s syndrome helicase unwinds G4 DNA. J Biol Chem. 1998;273:27587–92.PubMedCrossRefGoogle Scholar
  44. 44.
    Constantinou A, Tarsounas M, Karow JK, Brosh RM, Bohr VA, Hickson ID, West SC. Werner’s syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest. EMBO Rep. 2000;1:80–4.PubMedCrossRefGoogle Scholar
  45. 45.
    Karow JK, Constantinou A, Li JL, West SC, Hickson ID. The Bloom’s syndrome gene product promotes branch migration of holliday junctions. Proc Natl Acad Sci USA. 2000;97:6504–8.PubMedCrossRefGoogle Scholar
  46. 46.
    LeRoy G, Carroll R, Kyin S, Seki M, Cole MD. Identification of RecQL1 as a Holliday junction processing enzyme in human cell lines. Nucleic Acids Res. 2005;33:6251–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Xu D, Guo R, Sobeck A, Bachrati CZ, Yang J, Enomoto T, Brown GW, Hoatlin ME, Hickson ID, Wang W. RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability. Genes Dev. 2008;22:2843–55.PubMedCrossRefGoogle Scholar
  48. 48.
    Yin J, Sobeck A, Xu C, Meetei AR, Hoatlin M, Li L, Wang W. BLAP75, an essential component of Bloom’s syndrome protein complexes that maintain genome integrity. EMBO J. 2005;24:1465–76.PubMedCrossRefGoogle Scholar
  49. 49.
    Bussen W, Raynard S, Busygina V, Singh AK, Sung P. Holliday junction processing activity of the BLM-Topo IIIalpha-BLAP75 complex. J Biol Chem. 2007;282:31484–92.PubMedCrossRefGoogle Scholar
  50. 50.
    Raynard S, Zhao W, Bussen W, Lu L, Ding YY, Busygina V, Meetei AR, Sung P. Functional role of BLAP75 in BLM-topoisomerase IIIalpha-dependent holliday junction processing. J Biol Chem. 2008;283:15701–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Yang J, Bachrati CZ, Ou J, Hickson ID, Brown GW. Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is stimulated by BLM and RMI1. J Biol Chem. 2010;285:21426–36.PubMedCrossRefGoogle Scholar
  52. 52.
    Cejka P, Plank JL, Bachrati CZ, Hickson ID, Kowalczykowski SC. Rmi1 stimulates decatenation of double Holliday junctions during dissolution by Sgs1-Top3. Nat Struct Mol Biol. 2010;17:1377–82.PubMedCrossRefGoogle Scholar
  53. 53.
    Nimonkar AV, Genschel J, Kinoshita E, Polaczek P, Campbell JL, Wyman C, Modrich P, Kowalczykowski SC. BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev. 2011;25:350–62.PubMedCrossRefGoogle Scholar
  54. 54.
    Nimonkar AV, Ozsoy AZ, Genschel J, Modrich P, Kowalczykowski SC. Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair. Proc Natl Acad Sci USA. 2008;105:16906–11.PubMedCrossRefGoogle Scholar
  55. 55.
    Hu Y, Lu X, Barnes E, Yan M, Lou H, Luo G. Recql5 and Blm RecQ DNA helicases have nonredundant roles in suppressing crossovers. Mol Cell Biol. 2005;25:3431–42.PubMedCrossRefGoogle Scholar
  56. 56.
    Hu Y, Raynard S, Sehorn MG, Lu X, Bussen W, Zheng L, Stark JM, Barnes EL, Chi P, Janscak P, et al. RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments. Genes Dev. 2007;21:3073–84.PubMedCrossRefGoogle Scholar
  57. 57.
    Schwendener S, Raynard S, Paliwal S, Cheng A, Kanagaraj R, Shevelev I, Stark JM, Sung P, Janscak P. Physical interaction of RECQ5 helicase with RAD51 facilitates its anti-recombinase activity. J Biol Chem. 2010;285:15739–45.PubMedCrossRefGoogle Scholar
  58. 58.
    Islam MN, Fox 3rd D, Guo R, Enomoto T, Wang W. RecQL5 promotes genome stabilization through two parallel mechanisms—interacting with RNA polymerase II and acting as a helicase. Mol Cell Biol. 2010;30:2460–72.PubMedCrossRefGoogle Scholar
  59. 59.
    Kanagaraj R, Huehn D, MacKellar A, Menigatti M, Zheng L, Urban V, Shevelev I, Greenleaf AL, Janscak P. RECQ5 helicase associates with the C-terminal repeat domain of RNA polymerase II during productive elongation phase of transcription. Nucleic Acids Res. 2010;38:8131–40.PubMedCrossRefGoogle Scholar
  60. 60.
    Li M, Xu X, Liu Y. The SET2-RPB1 interaction domain of human RECQ5 is important for transcription-associated genome stability. Mol Cell Biol. 2011;31:2090–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Meetei AR, Medhurst AL, Ling C, Xue Y, Singh TR, Bier P, Steltenpool J, Stone S, Dokal I, Mathew CG, et al. A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nat Genet. 2005;37:958–63.PubMedCrossRefGoogle Scholar
  62. 62.
    Nishino T, Komori K, Ishino Y, Morikawa K. X-ray and biochemical anatomy of an archaeal XPF/Rad1/Mus81 family nuclease: similarity between its endonuclease domain and restriction enzymes. Structure. 2003;11:445–57.PubMedCrossRefGoogle Scholar
  63. 63.
    Nishino T, Komori K, Tsuchiya D, Ishino Y, Morikawa K. Crystal structure and functional implications of Pyrococcus furiosus hef helicase domain involved in branched DNA processing. Structure. 2005;13:143–53.PubMedCrossRefGoogle Scholar
  64. 64.
    Komori K, Hidaka M, Horiuchi T, Fujikane R, Shinagawa H, Ishino Y. Cooperation of the N-terminal Helicase and C-terminal endonuclease activities of Archaeal Hef protein in processing stalled replication forks. J Biol Chem. 2004;279:53175–85.PubMedCrossRefGoogle Scholar
  65. 65.
    Scheller J, Schurer A, Rudolph C, Hettwer S, Kramer W. MPH1, a yeast gene encoding a DEAH protein, plays a role in protection of the genome from spontaneous and chemically induced damage. Genetics. 2000;155:1069–81.PubMedGoogle Scholar
  66. 66.
    Schurer KA, Rudolph C, Ulrich HD, Kramer W. Yeast MPH1 gene functions in an error-free DNA damage bypass pathway that requires genes from Homologous recombination, but not from postreplicative repair. Genetics. 2004;166:1673–86.PubMedCrossRefGoogle Scholar
  67. 67.
    Choi K, Szakal B, Chen YH, Branzei D, Zhao X. The Smc5/6 complex and Esc2 influence multiple replication-associated recombination processes in Saccharomyces cerevisiae. Mol Biol Cell. 2010;21:2306–14.PubMedCrossRefGoogle Scholar
  68. 68.
    Chavez A, Agrawal V, Johnson FB. Homologous recombination-dependent rescue of deficiency in the structural maintenance of chromosomes (Smc) 5/6 complex. J Biol Chem. 2011;286:5119–25.PubMedCrossRefGoogle Scholar
  69. 69.
    Chen YH, Choi K, Szakal B, Arenz J, Duan X, Ye H, Branzei D, Zhao X. Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair. Proc Natl Acad Sci USA. 2009;106:21252–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Prakash R, Satory D, Dray E, Papusha A, Scheller J, Kramer W, Krejci L, Klein H, Haber JE, Sung P, et al. Yeast Mph1 helicase dissociates Rad51-made D-loops: implications for crossover control in mitotic recombination. Genes Dev. 2009;23:67–79.PubMedCrossRefGoogle Scholar
  71. 71.
    Prakash R, Krejci L, Van Komen S. Anke Schurer K, Kramer W, Sung P. Saccharomyces cerevisiae MPH1 gene, required for homologous recombination-mediated mutation avoidance, encodes a 3′ to 5′ DNA helicase. J Biol Chem. 2005;280:7854–60.PubMedCrossRefGoogle Scholar
  72. 72.
    Kang YH, Kang MJ, Kim JH, Lee CH, Cho IT, Hurwitz J, Seo YS. The MPH1 gene of Saccharomyces cerevisiae functions in Okazaki fragment processing. J Biol Chem. 2009;284:10376–86.PubMedCrossRefGoogle Scholar
  73. 73.
    Zheng XF, Prakash R, Saro D, Longerich S, Niu H, Sung P. Processing of DNA structures via DNA unwinding and branch migration by the S. cerevisiae Mph1 protein. DNA Repair (Amst). 2011;10:1034–43.CrossRefGoogle Scholar
  74. 74.
    Sun W, Nandi S, Osman F, Ahn JS, Jakovleska J, Lorenz A, Whitby MC. The FANCM ortholog Fml1 promotes recombination at stalled replication forks and limits crossing over during DNA double-strand break repair. Mol Cell. 2008;32:118–28.PubMedCrossRefGoogle Scholar
  75. 75.
    Kee Y, D’Andrea AD. Expanded roles of the Fanconi anemia pathway in preserving genomic stability. Genes Dev. 2010;24:1680–94.PubMedCrossRefGoogle Scholar
  76. 76.
    Gari K, Decaillet C, Delannoy M, Wu L, Constantinou A. Remodeling of DNA replication structures by the branch point translocase FANCM. Proc Natl Acad Sci USA. 2008;105:16107–12.PubMedCrossRefGoogle Scholar
  77. 77.
    Gari K, Decaillet C, Stasiak AZ, Stasiak A, Constantinou A. The Fanconi anemia protein FANCM can promote branch migration of Holliday junctions and replication forks. Mol Cell. 2008;29:141–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Rosado IV, Niedzwiedz W, Alpi AF, Patel KJ. The Walker B motif in avian FANCM is required to limit sister chromatid exchanges but is dispensable for DNA crosslink repair. Nucleic Acids Res. 2009;37:4360–70.PubMedCrossRefGoogle Scholar
  79. 79.
    Xue Y, Li Y, Guo R, Ling C, Wang W. FANCM of the Fanconi anemia core complex is required for both monoubiquitination and DNA repair. Hum Mol Genet. 2008;17:1641–52.PubMedCrossRefGoogle Scholar
  80. 80.
    Lawrence CW, Christensen RB. Metabolic suppressors of trimethoprim and ultraviolet light sensitivities of Saccharomyces cerevisiae rad6 mutants. J Bacteriol. 1979;139:866–76.PubMedGoogle Scholar
  81. 81.
    Nguyen MM, Livingston DM. The effect of a suppressed rad52 mutation on the suppression of rad6 by srs2. Yeast. 1997;13:1059–64.PubMedCrossRefGoogle Scholar
  82. 82.
    Palladino F, Klein HL. Analysis of mitotic and meiotic defects in Saccharomyces cerevisiae SRS2 DNA helicase mutants. Genetics. 1992;132:23–37.PubMedGoogle Scholar
  83. 83.
    Lee SK, Johnson RE, Yu SL, Prakash L, Prakash S. Requirement of yeast SGS1 and SRS2 genes for replication and transcription. Science. 1999;286:2339–42.PubMedCrossRefGoogle Scholar
  84. 84.
    Krejci L, Van Komen S, Li Y, Villemain J, Reddy MS, Klein H, Ellenberger T, Sung P. DNA helicase Srs2 disrupts the Rad51 presynaptic filament. Nature. 2003;423:305–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Van Komen S, Reddy MS, Krejci L, Klein H, Sung P. ATPase and DNA helicase activities of the Saccharomyces cerevisiae anti-recombinase Srs2. J Biol Chem. 2003;278:44331–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Veaute X, Jeusset J, Soustelle C, Kowalczykowski SC, Le Cam E, Fabre F. The Srs2 helicase prevents recombination by disrupting Rad51 nucleoprotein filaments. Nature. 2003;423:309–12.PubMedCrossRefGoogle Scholar
  87. 87.
    Antony E, Tomko EJ, Xiao Q, Krejci L, Lohman TM, Ellenberger T. Srs2 disassembles Rad51 filaments by a protein-protein interaction triggering ATP turnover and dissociation of Rad51 from DNA. Mol Cell. 2009;35:105–15.PubMedCrossRefGoogle Scholar
  88. 88.
    Colavito S, Macris-Kiss M, Seong C, Gleeson O, Greene EC, Klein HL, Krejci L, Sung P. Functional significance of the Rad51-Srs2 complex in Rad51 presynaptic filament disruption. Nucleic Acids Res. 2009;37:6754–64.PubMedCrossRefGoogle Scholar
  89. 89.
    Burgess RC, Lisby M, Altmannova V, Krejci L, Sung P, Rothstein R. Localization of recombination proteins and Srs2 reveals anti-recombinase function in vivo. J Cell Biol. 2009;185:969–81.PubMedCrossRefGoogle Scholar
  90. 90.
    Liu J, Renault L, Veaute X, Fabre F, Stahlberg H, Heyer WD. Rad51 paralogues Rad55-Rad57 balance the antirecombinase Srs2 in Rad51 filament formation. Nature. 2011; 479: 245–8.PubMedCrossRefGoogle Scholar
  91. 91.
    Moldovan GL, Pfander B, Jentsch S. PCNA, the maestro of the replication fork. Cell. 2007;129:665–79.PubMedCrossRefGoogle Scholar
  92. 92.
    Papouli E, Chen S, Davies AA, Huttner D, Krejci L, Sung P, Ulrich HD. Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p. Mol Cell. 2005;19:123–33.PubMedCrossRefGoogle Scholar
  93. 93.
    Pfander B, Moldovan GL, Sacher M, Hoege C, Jentsch S. SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase. Nature. 2005;436:428–33.PubMedGoogle Scholar
  94. 94.
    Armstrong AA, Mohideen F, Lima CD. Recognition of SUMO-modified PCNA requires tandem receptor motifs in Srs2. Nature. 2012;483:59–63.PubMedCrossRefGoogle Scholar
  95. 95.
    Barber LJ, Youds JL, Ward JD, McIlwraith MJ, O’Neil NJ, Petalcorin MI, Martin JS, Collis SJ, Cantor SB, Auclair M, et al. RTEL1 maintains genomic stability by suppressing homologous recombination. Cell. 2008;135:261–71.PubMedCrossRefGoogle Scholar
  96. 96.
    Ding H, Schertzer M, Wu X, Gertsenstein M, Selig S, Kammori M, Pourvali R, Poon S, Vulto I, Chavez E, et al. Regulation of murine telomere length by Rtel: an essential gene encoding a helicase-like protein. Cell. 2004;117:873–86.PubMedCrossRefGoogle Scholar
  97. 97.
    Youds JL, Mets DG, McIlwraith MJ, Martin JS, Ward JD, ONeil NJ, Rose AM, West SC, Meyer BJ, Boulton SJ. RTEL-1 enforces meiotic crossover interference and homeostasis. Science. 2010;327:1254–8.PubMedCrossRefGoogle Scholar
  98. 98.
    Lorenz A, Osman F, Folkyte V, Sofueva S, Whitby MC. Fbh1 limits Rad51-dependent recombination at blocked replication forks. Mol Cell Biol. 2009;29:4742–56.PubMedCrossRefGoogle Scholar
  99. 99.
    Osman F, Dixon J, Barr AR, Whitby MC. The F-Box DNA helicase Fbh1 prevents Rhp51-dependent recombination without mediator proteins. Mol Cell Biol. 2005;25:8084–96.PubMedCrossRefGoogle Scholar
  100. 100.
    Opresko PL, Sowd G, Wang H. The Werner syndrome helicase/exonuclease processes mobile D-loops through branch migration and degradation. PLoS One. 2009;4:e4825.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Molecular Biophysics and BiochemistryYale University School of MedicineNew HavenUSA

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