8-oxoG is one of the most common and mutagenic DNA base lesions caused by oxidative damage. However, it has not been possible to study the replication of a known 8-oxoG base in vivo in order to determine the accuracy of its replication, the influence of various components on that accuracy, and the extent to which an 8-oxoG might present a barrier to replication. We have been able to place a single 8-oxoG into the Saccharomyces cerevisiae chromosome in a defined location using single-strand oligonucleotide transformation and to study its replication in a fully normal chromosome context. During replication, 8-oxoG is recognized as a lesion and triggers a switch to translesion synthesis by Pol η, which replicates 8-oxoG with an accuracy (insertion of a C opposite the 8-oxoG) of approximately 94%. In the absence of Pol η, template switching to the newly synthesized sister chromatid is observed at least one third of the time; replication of the 8-oxoG in the absence of Pol η is less than 40% accurate. The mismatch repair (MMR) system plays an important role in 8-oxoG replication. Template switching is blocked by MMR and replication accuracy even in the absence of Pol η is approximately 95% when MMR is active. These findings indicate that in light of the overlapping mechanisms by which errors in 8-oxoG replication can be avoided in the cell, the mutagenic threat of 8-oxoG is due more to its abundance than the effect of a single lesion. In addition, the methods used here should be applicable to the study of any lesion that can be stably incorporated into synthetic oligonucleotides.
Vyšlo v časopise: Bypass of 8-oxodG. PLoS Genet 9(8): e32767. doi:10.1371/journal.pgen.1003682 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003682
1. EvansMD, DizdarogluM, CookeMS (2004) Oxidative DNA damage and disease: induction, repair and significance. Mutat Res 567 : 1–61.
2. BeardWA, BatraVK, WilsonSH (2010) DNA polymerase structure-based insight on the mutagenic properties of 8-oxoguanine. Mutat Res 703 : 18–23.
3. van LoonB, MarkkanenE, HubscherU (2010) Oxygen as a friend and enemy: How to combat the mutational potential of 8-oxo-guanine. DNA Repair (Amst) 9 : 604–616.
4. NashHM, BrunerSD, ScharerOD, KawateT, AddonaTA, et al. (1996) Cloning of a yeast 8-oxoguanine DNA glycosylase reveals the existence of a base-excision DNA-repair protein superfamily. Curr Biol 6 : 968–980.
5. van der KempPA, ThomasD, BarbeyR, de OliveiraR, BoiteuxS (1996) Cloning and expression in Escherichia coli of the OGG1 gene of Saccharomyces cerevisiae, which codes for a DNA glycosylase that excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine. Proc Natl Acad Sci USA 93 : 5197–5202.
6. GirardPM, D'HamC, CadetJ, BoiteuxS (1998) Opposite base-dependent excision of 7,8-dihydro-8-oxoadenine by the Ogg1 protein of Saccharomyces cerevisiae. Carcinogen 19 : 1299–1305.
7. EarleyMC, CrouseGF (1998) The role of mismatch repair in the prevention of base pair mutations in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 95 : 15487–15491.
8. NiTT, MarsischkyGT, KolodnerRD (1999) MSH2 and MSH6 are required for removal of adenine misincorporated opposite 8-oxo-guanine in S-cerevisiae. Mol Cell 4 : 439–444.
9. JanssonK, BlombergA, SunnerhagenP, Alm RosenbladM (2010) Evolutionary loss of 8-oxo-G repair components among eukaryotes. Genome Integr 1 : 12.
10. CarlsonKD, WashingtonAT (2005) Mechanism of efficient and accurate nucleotide incorporation opposite 7,8-dihydro-8-oxoguanine by Saccharomyces cerevisiae DNA polymerase eta. Mol Cell Biol 25 : 2169–2176.
11. HaracskaL, YuSL, JohnsonRE, PrakashL, PrakashS (2000) Efficient and accurate replication in the presence of 7,8-dihydro-8-oxoguanine by DNA polymerase eta. Nature Genet 25 : 458–461.
12. YuanFH, ZhangYB, RajpalDK, WuXH, GuoDY, et al. (2000) Specificity of DNA lesion bypass by the yeast DNA polymerase eta. J Biol Chem 275 : 8233–8239.
13. SilversteinTD, JainR, JohnsonRE, PrakashL, PrakashS, et al. (2010) Structural basis for error-free replication of oxidatively damaged DNA by yeast DNA polymerase η. Structure 18 : 1463–1470.
14. McCullochSD, KokoskaRJ, GargP, BurgersPM, KunkelTA (2009) The efficiency and fidelity of 8-oxo-guanine bypass by DNA polymerases δ and η. Nucleic Acids Res 37 : 2830–2840.
15. SabouriN, VibergJ, GoyalDK, JohanssonE, ChabesA (2008) Evidence for lesion bypass by yeast replicative DNA polymerases during DNA damage. Nucleic Acids Res 36 : 5660–5667.
16. De PadulaM, SlezakG, van der KempPA, BoiteuxS (2004) The post-replication repair RAD18 and RAD6 genes are involved in the prevention of spontaneous mutations caused by 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae. Nucleic Acids Res 32 : 5003–5010.
17. SakamotoAN, StoneJE, KisslingGE, McCullochSD, PavlovYI, et al. (2007) Mutator alleles of yeast DNA polymerase ζ. DNA Repair (Amst) 6 : 1829–1838.
18. van der KempPA, De PadulaM, Burguiere-SlezakG, UlrichHD, BoiteuxS (2009) PCNA monoubiquitylation and DNA polymerase η ubiquitin-binding domain are required to prevent 8-oxoguanine-induced mutagenesis in Saccharomyces cerevisiae. Nucleic Acids Res 37 : 2549–2559.
19. MudrakSV, Welz-VoegeleC, Jinks-RobertsonS (2009) The polymerase η translesion synthesis DNA polymerase acts independently of the mismatch repair system to limit mutagenesis caused by 7,8-dihydro-8-oxoguanine in yeast. Mol Cell Biol 29 : 5316–5326.
20. ChangDJ, CimprichKA (2009) DNA damage tolerance: when it's OK to make mistakes. Nat Chem Biol 5 : 82–90.
21. WatersLS, MinesingerBK, WiltroutME, D'SouzaS, WoodruffRV, et al. (2009) Eukaryotic translesion polymerases and their roles and regulation in DNA damage tolerance. Microbiol Mol Biol Rev 73 : 134–154.
22. DaigakuY, DaviesAA, UlrichHD (2010) Ubiquitin-dependent DNA damage bypass is separable from genome replication. Nature 465 : 951–955.
23. Nick McElhinnySA, GordeninDA, StithCM, BurgersPM, KunkelTA (2008) Division of labor at the eukaryotic replication fork. Mol Cell 30 : 137–144.
24. PavlovYI, NewlonCS, KunkelTA (2002) Yeast origins establish a strand bias for replicational mutagenesis. Mol Cell 10 : 207–213.
25. PavlovYI, MianIM, KunkelTA (2003) Evidence for preferential mismatch repair of lagging strand DNA replication errors in yeast. Curr Biol 13 : 744–748.
26. LiX, HeyerWD (2008) Homologous recombination in DNA repair and DNA damage tolerance. Cell Res 18 : 99–113.
27. MincaEC, KowalskiD (2010) Multiple Rad5 activities mediate sister chromatid recombination to bypass DNA damage at stalled replication forks. Mol Cell 38 : 649–661.
28. BlastyakA, PinterL, UnkI, PrakashL, PrakashS, et al. (2007) Yeast Rad5 protein required for postreplication repair has a DNA helicase activity specific for replication fork regression. Mol Cell 28 : 167–175.
29. KamiyaH, YamaguchiA, SuzukiT, HarashimaH (2010) Roles of specialized DNA polymerases in mutagenesis by 8-hydroxyguanine in human cells. Mutat Res 686 : 90–95.
30. SuzukiT, HarashimaH, KamiyaH (2010) Effects of base excision repair proteins on mutagenesis by 8-oxo-7,8-dihydroguanine (8-hydroxyguanine) paired with cytosine and adenine. DNA Repair (Amst) 9 : 542–550.
31. AvkinS, LivnehZ (2002) Efficiency, specificity and DNA polymerase-dependence of translesion replication across the oxidative DNA lesion 8-oxoguanine in human cells. Mutat Res 510 : 81–90.
32. MoriyaM, OuC, BodepudiV, JohnsonF, TakeshitaM, GrollmanAP (1991) Site-specific mutagenesis using a gapped duplex vector: a study of translesion synthesis past 8-oxodeoxyguanosine in E. coli. Mutat Res 254 : 281–288.
33. ScottAD, NeishaburyM, JonesDH, ReedSH, BoiteuxS, et al. (1999) Spontaneous mutation, oxidative DNA damage, and the roles of base and nucleotide excision repair in the yeast Saccharomyces cerevisiae. Yeast 15 : 205–218.
34. YamamotoT, MoerschellRP, WakemLP, FergusonD, ShermanF (1992) Parameters affecting the frequencies of transformation and co - transformation with synthetic oligonucleotides in yeast. Yeast 8 : 935–948.
35. YamamotoT, MoerschellRP, WakemLP, Komar-PanicucciS, ShermanF (1992) Strand-specificity in the transformation of yeast with synthetic oligonucleotides. Genetics 131 : 811–819.
36. BaoG, KowYW (2009) Effect of sequence context and direction of replication on AP site bypass in Saccharomyces cerevisiae. Mutat Res 669 : 147–154.
37. YungCW, OkugawaY, OtsukaC, OkamotoK, ArimotoS, et al. (2008) Influence of neighbouring base sequences on the mutagenesis induced by 7,8-dihydro-8-oxoguanine in yeast. Mutagenesis 23 : 509–513.
38. KowYW, BaoG, MinesingerB, Jinks-RobertsonS, SiedeW, et al. (2005) Mutagenic effects of abasic and oxidized abasic lesions in Saccharomyces cerevisiae. Nucleic Acids Res 33 : 6196–6202.
39. OtsukaC, KobayashiK, KawaguchiN, KunitomiN, MoriyamaK, et al. (2002) Use of yeast transformation by oligonucleotides to study DNA lesion bypass in vivo. Mutat Res 502 : 53–60.
40. OtsukaC, SanadaiS, HataY, OkutoH, NoskovVN, et al. (2002) Difference between deoxyribose - and tetrahydrofuran-type abasic sites in the in vivo mutagenic responses in yeast. Nucleic Acids Res 30 : 5129–5135.
41. NoskovV, NegishiK, OnoA, MatsudaA, OnoB, et al. (1994) Mutagenicity of 5-bromouracil and N6-hydroxyadenine studied by yeast oligonucleotide transformation assay. Mutat Res 308 : 43–51.
42. WilliamsT-M, FabbriRM, ReevesJW, CrouseGF (2005) A new reversion assay for measuring all possible base pair substitutions in Saccharomyces cerevisiae. Genetics 170 : 1423–1426.
43. RodriguezGP, SongJB, CrouseGF (2012) Transformation with oligonucleotides creating clustered changes in the yeast genome. PLoS ONE 7: e42905.
44. GirardPM, GuibourtN, BoiteuxS (1997) The Ogg1 protein of Saccharomyces cerevisiae: A 7,8-dihydro-8-oxoguanine DNA glycosylase AP lyase whose lysine 241 is a critical residue for catalytic activity. Nucleic Acids Res 25 : 3204–3211.
45. BoiteuxS, GellonL, GuibourtN (2002) Repair of 8-oxoguanine in Saccharomyces cerevisiae: interplay of DNA repair and replication mechanisms. Free Radic Biol Med 32 : 1244–1253.
46. DizdarogluM (2003) Substrate specificities and excision kinetics of DNA glycosylases involved in base-excision repair of oxidative DNA damage. Mutat Res 531 : 109–126.
47. BranzeiD, VanoliF, FoianiM (2008) SUMOylation regulates Rad18-mediated template switch. Nature 456 : 915–920.
48. ZhangH, LawrenceCW (2005) The error-free component of the RAD6/RAD18 DNA damage tolerance pathway of budding yeast employs sister-strand recombination. Proc Natl Acad Sci USA 102 : 15954–15959.
49. GhaemmaghamiS, HuhW, BowerK, HowsonRW, BelleA, et al. (2003) Global analysis of protein expression in yeast. Nature 425 : 737–741.
50. PavlovYI, ShcherbakovaPV (2010) DNA polymerases at the eukaryotic fork-20 years later. Mutat Res 685 : 45–53.
51. BoiteuxS, Jinks-RobertsonS (2013) DNA repair mechanisms and the bypass of DNA damage in Saccharomyces cerevisiae. Genetics 193 : 1025–1064.
52. UlrichHD, JentschS (2000) Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. EMBO J 19 : 3388–3397.
53. GangavarapuV, HaracskaL, UnkI, JohnsonRE, PrakashS, et al. (2006) Mms2-Ubc13-dependent and -independent roles of Rad5 ubiquitin ligase in postreplication repair and translesion DNA synthesis in Saccharomyces cerevisiae. Mol Cell Biol 26 : 7783–7790.
54. MinesingerBK, Jinks-RobertsonS (2005) Roles of RAD6 epistasis group members in spontaneous pol ζ-dependent translesion synthesis in Saccharomyces cerevisiae. Genetics 169 : 1939–1955.
55. StoriciF, LewisLK, ResnickMA (2001) In vivo site-directed mutagenesis using oligonucleotides. Nat Biotechnol 19 : 773–776.
56. WinzelerEA, ShoemakerDD, AstromoffA, LiangH, AndersonK, et al. (1999) Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285 : 901–906.
57. GoldsteinAL, McCuskerJH (1999) Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae. Yeast 15 : 1541–1553.
58. GüldenerU, HeckS, FiedlerT, BeinhauerJ, HegemannJH (1996) A new efficient gene disruption cassette for repeated use in budding yeast. Nucleic Acids Res 24 : 2519–2524.
59. KowYW, BaoG, ReevesJW, Jinks-RobertsonS, CrouseGF (2007) Oligonucleotide transformation of yeast reveals mismatch repair complexes to be differentially active on DNA replication strands. Proc Natl Acad Sci USA 104 : 11352–11357.
60. ShermanF (2002) Getting started with yeast. Methods Enzymol 350 : 3–41.
Zvýšte si kvalifikáciu online z pohodlia domova
Nemáte účet? Registrujte sa
Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
