Competition between Replicative and Translesion Polymerases during Homologous Recombination Repair in Drosophila

English version České info

In metazoans, the mechanism by which DNA is synthesized during homologous recombination repair of double-strand breaks is poorly understood. Specifically, the identities of the polymerase(s) that carry out repair synthesis and how they are recruited to repair sites are unclear. Here, we have investigated the roles of several different polymerases during homologous recombination repair in Drosophila melanogaster. Using a gap repair assay, we found that homologous recombination is impaired in Drosophila lacking DNA polymerase zeta and, to a lesser extent, polymerase eta. In addition, the Pol32 protein, part of the polymerase delta complex, is needed for repair requiring extensive synthesis. Loss of Rev1, which interacts with multiple translesion polymerases, results in increased synthesis during gap repair. Together, our findings support a model in which translesion polymerases and the polymerase delta complex compete during homologous recombination repair. In addition, they establish Rev1 as a crucial factor that regulates the extent of repair synthesis.

Vyšlo v časopise: Competition between Replicative and Translesion Polymerases during Homologous Recombination Repair in Drosophila. PLoS Genet 8(4): e32767. doi:10.1371/journal.pgen.1002659
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002659

Souhrn

Zdroje

1. LieberMR 2010 The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 79 181 211

2. HicksWMKimMHaberJE 2010 Increased mutagenesis and unique mutation signature associated with mitotic gene conversion. Science 329 82 85

3. HolbeckSLStrathernJN 1997 A role for REV3 in mutagenesis during double-strand break repair in Saccharomyces cerevisiae. Genetics 147 1017 1024

4. HeyerWDEhmsenKTLiuJ 2010 Regulation of homologous recombination in eukaryotes. Annu Rev Genet 44 113 139

5. NassifNPenneyJPalSEngelsWRGloorGB 1994 Efficient copying of nonhomologous sequences from ectopic sites via P-element-induced gap repair. Mol Cell Biol 14 1613 1625

6. McCullochSDKunkelTA 2008 The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases. Cell Res 18 148 161

7. LehmannARNiimiAOgiTBrownSSabbionedaS 2007 Translesion synthesis: Y-family polymerases and the polymerase switch. DNA Repair (Amst) 6 891 899

8. TakataKWoodRD 2009 Bypass specialists operate together. EMBO J 28 313 314

9. PloskyBSWoodgateR 2004 Switching from high-fidelity replicases to low-fidelity lesion-bypass polymerases. Curr Opin Genet Dev 14 113 119

10. HolmesAMHaberJE 1999 Double-strand break repair in yeast requires both leading and lagging strand DNA polymerases. Cell 96 415 424

11. LydeardJRLipkin-MooreZSheuYJStillmanBBurgersPM 2010 Break-induced replication requires all essential DNA replication factors except those specific for pre-RC assembly. Genes Dev 24 1133 1144

12. MaloiselLFabreFGangloffS 2008 DNA polymerase delta is preferentially recruited during homologous recombination to promote heteroduplex DNA extension. Mol Cell Biol 28 1373 1382

13. LiXStithCMBurgersPMHeyerWD 2009 PCNA is required for initiation of recombination-associated DNA synthesis by DNA polymerase delta. Mol Cell 36 704 713

14. LydeardJRJainSYamaguchiMHaberJE 2007 Break-induced replication and telomerase-independent telomere maintenance require Pol32. Nature 448 820 823

15. KawamotoTArakiKSonodaEYamashitaYMHaradaK 2005 Dual roles for DNA polymerase eta in homologous DNA recombination and translesion DNA synthesis. Mol Cell 20 793 799

16. SonodaEOkadaTZhaoGYTateishiSArakiK 2003 Multiple roles of Rev3, the catalytic subunit of polzeta in maintaining genome stability in vertebrates. Embo J 22 3188 3197

17. McIlwraithMJVaismanALiuYFanningEWoodgateR 2005 Human DNA polymerase eta promotes DNA synthesis from strand invasion intermediates of homologous recombination. Mol Cell 20 783 792

18. McIlwraithMJWestSC 2008 DNA repair synthesis facilitates RAD52-mediated second-end capture during DSB repair. Mol Cell 29 510 516

19. HiranoYSugimotoK 2006 ATR homolog Mec1 controls association of DNA polymerase zeta-Rev1 complex with regions near a double-strand break. Curr Biol 16 586 590

20. RattrayAJShaferBKMcGillCBStrathernJN 2002 The roles of REV3 and RAD57 in double-strand-break-repair-induced mutagenesis of Saccharomyces cerevisiae. Genetics 162 1063 1077

21. GrayFCPohlerJRWarbrickEMacNeillSA 2004 Mapping and mutation of the conserved DNA polymerase interaction motif (DPIM) located in the C-terminal domain of fission yeast DNA polymerase delta subunit Cdc27. BMC Mol Biol 5 21

22. GerikKJLiXPautzABurgersPM 1998 Characterization of the two small subunits of Saccharomyces cerevisiae DNA polymerase delta. J Biol Chem 273 19747 19755

23. McVeyMAdamsMStaeva-VieiraESekelskyJJ 2004 Evidence for multiple cycles of strand invasion during repair of double-strand gaps in Drosophila. Genetics 167 699 705

24. AdamsMDMcVeyMSekelskyJJ 2003 Drosophila BLM in double-strand break repair by synthesis-dependent strand annealing. Science 299 265 267

25. GibbsPEMcDonaldJWoodgateRLawrenceCW 2005 The relative roles in vivo of Saccharomyces cerevisiae Pol eta, Pol zeta, Rev1 protein and Pol32 in the bypass and mutation induction of an abasic site, T-T (6-4) photoadduct and T-T cis-syn cyclobutane dimer. Genetics 169 575 582

26. IshikawaTUematsuNMizukoshiTIwaiSIwasakiH 2001 Mutagenic and nonmutagenic bypass of DNA lesions by Drosophila DNA polymerases dpoleta and dpoliota. J Biol Chem 276 15155 15163

27. KosarekJNWoodruffRVRivera-BegemanAGuoCD'SouzaS 2008 Comparative analysis of in vivo interactions between Rev1 protein and other Y-family DNA polymerases in animals and yeasts. DNA Repair (Amst) 7 439 451

28. GuoCFischhaberPLLuk-PaszycMJMasudaYZhouJ 2003 Mouse Rev1 protein interacts with multiple DNA polymerases involved in translesion DNA synthesis. Embo J 22 6621 6630

29. AcharyaNJohnsonREPagesVPrakashLPrakashS 2009 Yeast Rev1 protein promotes complex formation of DNA polymerase zeta with Pol32 subunit of DNA polymerase delta. Proc Natl Acad Sci U S A 106 9631 9636

30. WatersLSWalkerGC 2006 The critical mutagenic translesion DNA polymerase Rev1 is highly expressed during G(2)/M phase rather than S phase. Proc Natl Acad Sci U S A 103 8971 8976

31. RichardsonCJasinM 2000 Coupled homologous and nonhomologous repair of a double-strand break preserves genomic integrity in mammalian cells. Mol Cell Biol 20 9068 9075

32. JohanssonEGargPBurgersPM 2004 The Pol32 subunit of DNA polymerase delta contains separable domains for processive replication and proliferating cell nuclear antigen (PCNA) binding. J Biol Chem 279 1907 1915

33. SmithCELamAFSymingtonLS 2009 Aberrant double-strand break repair resulting in half crossovers in mutants defective for Rad51 or the DNA polymerase delta complex. Mol Cell Biol 29 1432 1441

34. de GrooteFHJansenJGMasudaYShahDMKamiyaK 2011 The Rev1 translesion synthesis polymerase has multiple distinct DNA binding modes. DNA Repair (Amst) 10 915 925

35. SmithCELlorenteBSymingtonLS 2007 Template switching during break-induced replication. Nature 447 102 105

36. Johnson-SchlitzDMEngelsWR 2006 The effect of gap length on double-strand break repair in Drosophila. Genetics 173 2033 2038

37. AndersenPLXuFZiolaBMcGregorWGXiaoW 2011 Sequential assembly of translesion DNA polymerases at UV-induced DNA damage sites. Mol Biol Cell 22 2373 2383

38. KohzakiMNishiharaKHirotaKSonodaEYoshimuraM 2010 DNA polymerases nu and theta are required for efficient immunoglobulin V gene diversification in chicken. J Cell Biol 189 1117 1127

39. OgiTLimsirichaikulSOvermeerRMVolkerMTakenakaK 2010 Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Mol Cell 37 714 727

40. HoTVScharerOD 2010 Translesion DNA synthesis polymerases in DNA interstrand crosslink repair. Environ Mol Mutagen 51 552 566

41. SharmaSHicksJKChuteCLBrennanJRAhnJY 2012 REV1 and polymerase zeta facilitate homologous recombination repair. Nucleic Acids Res 40 682 691

42. WitsellAKaneDPRubinSMcVeyM 2009 Removal of the Bloom Syndrome DNA helicase extends the utility of imprecise transposon excision for making null mutations in Drosophila. Genetics 183 1187 1193

43. McVeyM 2010 In vivo analysis of Drosophila BLM helicase function during DNA double-strand gap repair. Methods Mol Biol 587 185 194

44. GloorGBPrestonCRJohnson-SchlitzDMNassifNAPhillisRW 1993 Type I repressors of P element mobility. Genetics 135 81 95