DNA Polymerase ζ-Dependent Lesion Bypass in Is Accompanied by Error-Prone Copying of Long Stretches of Adjacent DNA

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Genomic instability is associated with multiple genetic diseases. Endogenous and exogenous DNA-damaging factors constitute a major source of genomic instability. Mutations occur when DNA lesions are bypassed by specialized translesion synthesis (TLS) DNA polymerases that are less accurate than the normal replicative polymerases. The discovery of the remarkable infidelity of the TLS enzymes at the turn of the century immediately suggested that their contribution to replication must be tightly restricted to sites of DNA damage to avoid excessive mutagenesis. The actual extent of error-prone synthesis that accompanies TLS in vivo has never been estimated. We describe a novel genetic approach to measure the length of DNA synthesized by TLS polymerases upon their recruitment to sites of DNA damage. We show that stretches of error-prone synthesis associated with the bypass of a single damaged nucleotide span at least 200 and sometimes up to 1,000 nucleotide-long segments, resulting in more than a 300,000-fold increase in mutagenesis in the surrounding region. We speculate that processive synthesis of long DNA stretches by error-prone polymerases could contribute to clustered mutagenesis, a phenomenon that allows for rapid genome changes without significant loss of fitness and plays an important role in tumorigenesis, the immune response and adaptation.

Vyšlo v časopise: DNA Polymerase ζ-Dependent Lesion Bypass in Is Accompanied by Error-Prone Copying of Long Stretches of Adjacent DNA. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005110
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005110

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1. McCulloch SD, Kunkel TA. The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases. Cell Res. 2008;18 : 148–161. doi: 10.1038/cr.2008.4 18166979

2. Broyde S, Wang L, Rechkoblit O, Geacintov NE, Patel DJ. Lesion processing: high-fidelity versus lesion-bypass DNA polymerases. Trends Biochem Sci. 2008;33 : 209–219. doi: 10.1016/j.tibs.2008.02.004 18407502

3. Boiteux S, Jinks-Robertson S. DNA repair mechanisms and the bypass of DNA damage in Saccharomyces cerevisiae. Genetics. 2013;193 : 1025–1064. doi: 10.1534/genetics.112.145219 23547164

4. Yang W. An Overview of Y-Family DNA Polymerases and a Case Study of Human DNA Polymerase η. Biochemistry. 2014;53 : 2793–2803. doi: 10.1021/bi500019s 24716551

5. Sale JE, Lehmann AR, Woodgate R. Y-family DNA polymerases and their role in tolerance of cellular DNA damage. Nat Rev Mol Cell Biol. 2012;13 : 141–152. doi: 10.1038/nrm3289 22358330

6. Waters LS, Minesinger BK, Wiltrout ME, D'Souza S, Woodruff RV, Walker GC. Eukaryotic translesion polymerases and their roles and regulation in DNA damage tolerance. Microbiol Mol Biol Rev. 2009;73 : 134–154. doi: 10.1128/MMBR.00034-08 19258535

7. Lange SS, Takata K, Wood RD. DNA polymerases and cancer. Nat Rev Cancer. 2011;11 : 96–110. doi: 10.1038/nrc2998 21258395

8. Lawrence CW. Cellular functions of DNA polymerase ζ and Rev1 protein. Adv Protein Chem. 2004;69 : 167–203. 15588843

9. Prakash S, Johnson RE, Prakash L. Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu Rev Biochem. 2005;74 : 317–353. 15952890

10. Livneh Z, Ziv O, Shachar S. Multiple two-polymerase mechanisms in mammalian translesion DNA synthesis. Cell Cycle. 2010;9 : 729–735. 20139724

11. Lehmann AR, Fuchs RP. Gaps and forks in DNA replication: Rediscovering old models. DNA Repair (Amst). 2006;5 : 1495–1498. 16956796

12. Fujii S, Fuchs RP. Defining the position of the switches between replicative and bypass DNA polymerases. EMBO J. 2004;23 : 4342–4352. 15470496

13. McCulloch SD, Kokoska RJ, Chilkova O, Welch CM, Johansson E, Burgers PM, et al. Enzymatic switching for efficient and accurate translesion DNA replication. Nucleic Acids Res. 2004;32 : 4665–4675. 15333698

14. Ulrich HD. Timing and spacing of ubiquitin-dependent DNA damage bypass. FEBS Lett. 2011;585 : 2861–2867. doi: 10.1016/j.febslet.2011.05.028 21605556

15. Elvers I, Johansson F, Groth P, Erixon K, Helleday T. UV stalled replication forks restart by re-priming in human fibroblasts. Nucleic Acids Res. 2011;39 : 7049–7057. doi: 10.1093/nar/gkr420 21646340

16. Callegari AJ, Clark E, Pneuman A, Kelly TJ. Postreplication gaps at UV lesions are signals for checkpoint activation. Proc Natl Acad Sci USA. 2010;107 : 8219–8224. doi: 10.1073/pnas.1003449107 20404181

17. Lopes M, Foiani M, Sogo JM. Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions. Mol Cell. 2006;21 : 15–27. 16387650

18. Rupp WD, Howard-Flanders P. Discontinuities in the DNA synthesized in an excision-defective strain of Escherichia coli following ultraviolet irradiation. J Mol Biol. 1968;31 : 291–304. 4865486

19. Iyer VN, Rupp WD. Usefulness of benzoylated naphthoylated DEAE-cellulose to distinguish and fractionate double-stranded DNA bearing different extents of single-stranded regions. Biochim Biophys Acta. 1971;228 : 117–126. 4926026

20. Prakash L. Characterization of postreplication repair in Saccharomyces cerevisiae and effects of rad6, rad18, rev3 and rad52 mutations. Mol Gen Genet. 1981;184 : 471–478. 7038396

21. Lehmann AR. Postreplication repair of DNA in ultraviolet-irradiated mammalian cells. J Mol Biol. 1972;66 : 319–337. 5037019

22. Meneghini R. Gaps in DNA synthesized by ultraviolet light-irradiated WI38 human cells. Biochim Biophys Acta. 1976;425 : 419–427. 130925

23. Ogi T, Limsirichaikul S, Overmeer RM, Volker M, Takenaka K, Cloney R, et al. Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Mol Cell. 2010;37 : 714–727. doi: 10.1016/j.molcel.2010.02.009 20227374

24. Kozmin SG, Jinks-Robertson S. The mechanism of nucleotide excision repair-mediated UV-induced mutagenesis in nonproliferating cells. Genetics. 2013;193 : 803–817. doi: 10.1534/genetics.112.147421 23307894

25. Zhang Y, Wu X, Guo D, Rechkoblit O, Geacintov NE, Wang Z. Two-step error-prone bypass of the (+) -⁠ and (-)-trans-anti-BPDE-N2-dG adducts by human DNA polymerases η and κ. Mutat Res. 2002;510 : 23–35. 12459440

26. Ruiz-Rubio M, Bridges BA. Mutagenic DNA repair in Escherichia coli. XIV. Influence of two DNA polymerase III mutator alleles on spontaneous and UV mutagenesis. Mol Gen Genet. 1987;208 : 542–548. 3312950

27. Maor-Shoshani A, Reuven NB, Tomer G, Livneh Z. Highly mutagenic replication by DNA polymerase V (UmuC) provides a mechanistic basis for SOS untargeted mutagenesis. Proc Natl Acad Sci USA. 2000;97 : 565–570. 10639119

28. Zhong X, Garg P, Stith CM, Nick McElhinny SA, Kissling GE, Burgers PM, et al. The fidelity of DNA synthesis by yeast DNA polymerase ζ alone and with accessory proteins. Nucleic Acids Res. 2006;34 : 4731–4742. 16971464

29. Haracska L, Unk I, Johnson RE, Johansson E, Burgers PM, Prakash S, et al. Roles of yeast DNA polymerases δ and ζ and of Rev1 in the bypass of abasic sites. Genes Dev. 2001;15 : 945–954. 11316789

30. Gibbs PE, Lawrence CW. Novel mutagenic properties of abasic sites in Saccharomyces cerevisiae. J Mol Biol. 1995;251 : 229–236. 7643399

31. Pages V, Johnson RE, Prakash L, Prakash S. Mutational specificity and genetic control of replicative bypass of an abasic site in yeast. Proc Natl Acad Sci USA. 2008;105 : 1170–1175. doi: 10.1073/pnas.0711227105 18202176

32. Kow YW, Bao G, Minesinger B, Jinks-Robertson S, Siede W, Jiang YL, et al. Mutagenic effects of abasic and oxidized abasic lesions in Saccharomyces cerevisiae. Nucleic Acids Res. 2005;33 : 6196–6202. 16257982

33. Zhao B, Xie Z, Shen H, Wang Z. Role of DNA polymerase η in the bypass of abasic sites in yeast cells. Nucleic Acids Res. 2004;32 : 3984–3994. 15284331

34. Torres-Ramos CA, Johnson RE, Prakash L, Prakash S. Evidence for the involvement of nucleotide excision repair in the removal of abasic sites in yeast. Mol Cell Biol. 2000;20 : 3522–3528. 10779341

35. Lehner K, Jinks-Robertson S. The mismatch repair system promotes DNA polymerase ζ-dependent translesion synthesis in yeast. Proc Natl Acad Sci USA. 2009;106 : 5749–5754. doi: 10.1073/pnas.0812715106 19307574

36. Ravanat JL, Douki T, Cadet J. Direct and indirect effects of UV radiation on DNA and its components. J Photochem Photobiol B. 2001;63 : 88–102. 11684456

37. Gibbs PE, McDonald J, Woodgate R, Lawrence CW. The relative roles in vivo of Saccharomyces cerevisiae Pol η, Pol ζ, 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. 2005;169 : 575–582. 15520252

38. Kozmin SG, Pavlov YI, Kunkel TA, Sage E. Roles of Saccharomyces cerevisiae DNA polymerases Polη and Polζ in response to irradiation by simulated sunlight. Nucleic Acids Res. 2003;31 : 4541–4552. 12888515

39. Yu SL, Johnson RE, Prakash S, Prakash L. Requirement of DNA polymerase η for error-free bypass of UV-induced CC and TC photoproducts. Mol Cell Biol. 2001;21 : 185–188. 11113193

40. Budd ME, Campbell JL. DNA polymerases required for repair of UV-induced damage in Saccharomyces cerevisiae. Mol Cell Biol. 1995;15 : 2173–2179. 7891712

41. Unrau P, Wheatcroft R, Cox B, Olive T. The formation of pyrimidine dimers in the DNA of fungi and bacteria. Biochim Biophys Acta. 1973;312 : 626–632. 4200353

42. Guo D, Wu X, Rajpal DK, Taylor JS, Wang Z. Translesion synthesis by yeast DNA polymerase ζ from templates containing lesions of ultraviolet radiation and acetylaminofluorene. Nucleic Acids Res. 2001;29 : 2875–2883. 11433034

43. Abdulovic AL, Jinks-Robertson S. The in vivo characterization of translesion synthesis across UV-induced lesions in Saccharomyces cerevisiae: insights into Pol ζ -⁠ and Pol η-dependent frameshift mutagenesis. Genetics. 2006;172 : 1487–1498. 16387871

44. Nelson JR, Lawrence CW, Hinkle DC. Thymine-thymine dimer bypass by yeast DNA polymerase ζ. Science. 1996;272 : 1646–1649. 8658138

45. Johnson RE, Washington MT, Haracska L, Prakash S, Prakash L. Eukaryotic polymerases ι and ζ act sequentially to bypass DNA lesions. Nature. 2000;406 : 1015–1019. 10984059

46. Acharya N, Johnson RE, Prakash S, Prakash L. Complex formation with Rev1 enhances the proficiency of Saccharomyces cerevisiae DNA polymerase ζ for mismatch extension and for extension opposite from DNA lesions. Mol Cell Biol. 2006;26 : 9555–9563. 17030609

47. Bresson A, Fuchs RP. Lesion bypass in yeast cells: Pol η participates in a multi-DNA polymerase process. EMBO J. 2002;21 : 3881–3887. 12110599

48. Yang Y, Sterling J, Storici F, Resnick MA, Gordenin DA. Hypermutability of damaged single-strand DNA formed at double-strand breaks and uncapped telomeres in yeast Saccharomyces cerevisiae. PLoS Genet. 2008;4: e1000264. doi: 10.1371/journal.pgen.1000264 19023402

49. Smith DJ, Whitehouse I. Intrinsic coupling of lagging-strand synthesis to chromatin assembly. Nature. 2012;483 : 434–438. doi: 10.1038/nature10895 22419157

50. Waisertreiger IS, Liston VG, Menezes MR, Kim HM, Lobachev KS, Stepchenkova EI, et al. Modulation of mutagenesis in eukaryotes by DNA replication fork dynamics and quality of nucleotide pools. Environ Mol Mutagen. 2012;53 : 699–724. doi: 10.1002/em.21735 23055184

51. Greenfeder SA, Newlon CS. Replication forks pause at yeast centromeres. Mol Cell Biol. 1992;12 : 4056–4066. 1508202

52. Fachinetti D, Bermejo R, Cocito A, Minardi S, Katou Y, Kanoh Y, et al. Replication termination at eukaryotic chromosomes is mediated by Top2 and occurs at genomic loci containing pausing elements. Mol Cell. 2010;39 : 595–605. doi: 10.1016/j.molcel.2010.07.024 20797631

53. McGuffee SR, Smith DJ, Whitehouse I. Quantitative, genome-wide analysis of eukaryotic replication initiation and termination. Mol Cell. 2013;50 : 123–135. doi: 10.1016/j.molcel.2013.03.004 23562327

54. Drake JW. A constant rate of spontaneous mutation in DNA-based microbes. Proc Natl Acad Sci USA. 1991;88 : 7160–7164. 1831267

55. Nik-Zainal S, Alexandrov LB, Wedge DC, Van Loo P, Greenman CD, Raine K, et al. Mutational processes molding the genomes of 21 breast cancers. Cell. 2012;149 : 979–993. doi: 10.1016/j.cell.2012.04.024 22608084

56. Roberts SA, Sterling J, Thompson C, Harris S, Mav D, Shah R, et al. Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions. Mol Cell. 2012;46 : 424–435. doi: 10.1016/j.molcel.2012.03.030 22607975

57. Taylor BJ, Nik-Zainal S, Wu YL, Stebbings LA, Raine K, Campbell PJ, et al. DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis. Elife. 2013;2: e00534. doi: 10.7554/eLife.00534 23599896

58. Camps M, Herman A, Loh E, Loeb LA. Genetic constraints on protein evolution. Crit Rev Biochem Mol Biol. 2007;42 : 313–326. 17917869

59. Stone JE, Lujan SA, Kunkel TA, Kunkel TA. DNA polymerase ζ generates clustered mutations during bypass of endogenous DNA lesions in Saccharomyces cerevisiae. Environ Mol Mutagen. 2012;53 : 777–786. doi: 10.1002/em.21728 22965922

60. Drake JW, Bebenek A, Kissling GE, Peddada S. Clusters of mutations from transient hypermutability. Proc Natl Acad Sci USA. 2005;102 : 12849–12854. 16118275

61. Crosby B, Prakash L, Davis H, Hinkle DC. Purification and characterization of a uracil-DNA glycosylase from the yeast Saccharomyces cerevisiae. Nucleic Acids Res. 1981;9 : 5797–5809. 7031606

62. Sharma S, Shah NA, Joiner AM, Roberts KH, Canman CE. DNA polymerase ζ is a major determinant of resistance to platinum-based chemotherapeutic agents. Mol Pharmacol. 2012;81 : 778–787. doi: 10.1124/mol.111.076828 22387291

63. Doles J, Oliver TG, Cameron ER, Hsu G, Jacks T, Walker GC, et al. Suppression of Rev3, the catalytic subunit of Polζ, sensitizes drug-resistant lung tumors to chemotherapy. Proc Natl Acad Sci USA. 2010;107 : 20786–20791. doi: 10.1073/pnas.1011409107 21068376

64. Okuda T, Lin X, Trang J, Howell SB. Suppression of hREV1 expression reduces the rate at which human ovarian carcinoma cells acquire resistance to cisplatin. Mol Pharmacol. 2005;67 : 1852–1860. 15758147

65. Xie K, Doles J, Hemann MT, Walker GC. Error-prone translesion synthesis mediates acquired chemoresistance. Proc Natl Acad Sci USA. 2010;107 : 20792–20797. doi: 10.1073/pnas.1011412107 21068378

66. Shcherbakova PV, Noskov VN, Pshenichnov MR, Pavlov YI. Base analog 6-N-hydroxylaminopurine mutagenesis in the yeast Saccharomyces cerevisiae is controlled by replicative DNA polymerases. Mutat Res. 1996;369 : 33–44. 8700180

67. Shcherbakova PV, Pavlov YI. 3'—>5' exonucleases of DNA polymerases ε and δ correct base analog induced DNA replication errors on opposite DNA strands in Saccharomyces cerevisiae. Genetics. 1996;142 : 717–726. 8849882

68. Gueldener U, Heinisch J, Koehler GJ, Voss D, Hegemann JH. A second set of loxP marker cassettes for Cre-mediated multiple gene knockouts in budding yeast. Nucleic Acids Res. 2002;30: e23. 11884642

69. Guldener U, Heck S, Fielder T, Beinhauer J, Hegemann JH. A new efficient gene disruption cassette for repeated use in budding yeast. Nucleic Acids Res. 1996;24 : 2519–2524. 8692690

70. Shcherbakova PV, Kunkel TA. Mutator phenotypes conferred by MLH1 overexpression and by heterozygosity for mlh1 mutations. Mol Cell Biol. 1999;19 : 3177–3183. 10082584

71. Shcherbakova PV, Pavlov YI. Mutagenic specificity of the base analog 6-N-hydroxylaminopurine in the URA3 gene of the yeast Saccharomyces cerevisiae. Mutagenesis. 1993;8 : 417–421. 8231822

72. Lada AG, Waisertreiger IS, Grabow CE, Prakash A, Borgstahl GE, Rogozin IB, et al. Replication protein A (RPA) hampers the processive action of APOBEC3G cytosine deaminase on single-stranded DNA. PLoS One. 2011;6: e24848. doi: 10.1371/journal.pone.0024848 21935481

73. Sikorski RS, Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989;122 : 19–27. 2659436

74. Banerjee SK, Borden A, Christensen RB, LeClerc JE, Lawrence CW. SOS-dependent replication past a single trans-syn T-T cyclobutane dimer gives a different mutation spectrum and increased error rate compared with replication past this lesion in uninduced cells. J Bacteriol. 1990;172 : 2105–2112. 2180917

75. Wang Z, Rossman TG. Isolation of DNA fragments from agarose gel by centrifugation. Nucleic Acids Res. 1994;22 : 2862–2863. 7519772

76. Amberg DC, Burke DJ, Strathern JN. High-efficiency transformation of yeast. CSH Protoc. 2006;2006.

77. Northam MR, Robinson HA, Kochenova OV, Shcherbakova PV. Participation of DNA polymerase ζ in replication of undamaged DNA in Saccharomyces cerevisiae. Genetics. 2010;184 : 27–42. doi: 10.1534/genetics.109.107482 19841096

78. Drake JW, Charlesworth B, Charlesworth D, Crow JF. Rates of spontaneous mutation. Genetics. 1998;148 : 1667–1686. 9560386