Oxidative Stress and Replication-Independent DNA Breakage Induced by Arsenic in

English version České info

Arsenic is a well-established human carcinogen of poorly understood mechanism of genotoxicity. It is generally accepted that arsenic acts indirectly by generating oxidative DNA damage that can be converted to replication-dependent DNA double-strand breaks (DSBs), as well as by interfering with DNA repair pathways and DNA methylation. Here we show that in budding yeast arsenic also causes replication and transcription-independent DSBs in all phases of the cell cycle, suggesting a direct genotoxic mode of arsenic action. This is accompanied by DNA damage checkpoint activation resulting in cell cycle delays in S and G2/M phases in wild type cells. In G1 phase, arsenic activates DNA damage response only in the absence of the Yku70–Yku80 complex which normally binds to DNA ends and inhibits resection of DSBs. This strongly indicates that DSBs are produced by arsenic in G1 but DNA ends are protected by Yku70–Yku80 and thus invisible for the checkpoint response. Arsenic-induced DSBs are processed by homologous recombination (HR), as shown by Rfa1 and Rad52 nuclear foci formation and requirement of HR proteins for cell survival during arsenic exposure. We show further that arsenic greatly sensitizes yeast to phleomycin as simultaneous treatment results in profound accumulation of DSBs. Importantly, we observed a similar response in fission yeast Schizosaccharomyces pombe, suggesting that the mechanisms of As(III) genotoxicity may be conserved in other organisms.

Vyšlo v časopise: Oxidative Stress and Replication-Independent DNA Breakage Induced by Arsenic in. PLoS Genet 9(7): e32767. doi:10.1371/journal.pgen.1003640
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003640

Souhrn

Zdroje

1. TapioS, GroscheB (2006) Arsenic in the aetiology of cancer. Mutat Res 612 : 215–246.

2. DildaPJ, HoggPJ (2007) Arsenical-based cancer drugs. Cancer Treat Rev 33 : 542–564.

3. MurrayHW, BermanJD, DaviesCR, SaraviaNG (2005) Advances in leishmaniasis. Lancet 366 : 1561–1577.

4. MartinezVD, VucicEA, Becker-SantosDD, GilL, LamWL (2011) Arsenic exposure and the induction of human cancers. J Toxicol 2011 : 431287.

5. LiuJX, ZhouGB, ChenSJ, ChenZ (2012) Arsenic compounds: revived ancient remedies in the fight against human malignancies. Curr Opin Chem Biol 16 : 92–98.

6. RossmanTG, KleinCB (2011) Genetic and epigenetic effects of environmental arsenicals. Metallomics 3 : 1135–1141.

7. KesselM, LiuSX, XuA, SantellaR, HeiTK (2002) Arsenic induces oxidative DNA damage in mammalian cells. Mol Cell Biochem 234–235 : 301–308.

8. LynnS, LaiHT, GurrJR, JanKY (1997) Arsenite retards DNA break rejoining by inhibiting DNA ligation. Mutagenesis 12 : 353–358.

9. SykoraP, SnowET (2008) Modulation of DNA polymerase beta-dependent base excision repair in cultured human cells after low dose exposure to arsenite. Toxicol Appl Pharmacol 228 : 385–394.

10. AndrewAS, KaragasMR, HamiltonJW (2003) Decreased DNA repair gene expression among individuals exposed to arsenic in United States drinking water. Int J Cancer 104 : 263–268.

11. DingW, LiuW, CooperKL, QinXJ, de Souza BergoPL, et al. (2009) Inhibition of poly(ADP-ribose) polymerase-1 by arsenite interferes with repair of oxidative DNA damage. J Biol Chem 284 : 6809–6817.

12. ZhouX, SunX, CooperKL, WangF, LiuKJ, et al. (2011) Arsenite interacts selectively with zinc finger proteins containing C3H1 or C4 motifs. J Biol Chem 286 : 22855–22863.

13. YingS, MyersK, BottomleyS, HelledayT, BryantHE (2009) BRCA2-dependent homologous recombination is required for repair of arsenite-induced replication lesions in mammalian cells. Nucleic Acids Res 37 : 5105–5113.

14. ZhangX, YangF, ShimJY, KirkKL, AndersonDE, et al. (2007) Identification of arsenic-binding proteins in human breast cancer cells. Cancer Lett 255 : 95–106.

15. RamírezT, StopperH, FischerT, HockR, HerreraLA (2008) S-adenosyl-L-methionine counteracts mitotic disturbances and cytostatic effects induced by sodium arsenite in HeLa cells. Mutat Res 637 : 152–160.

16. MigdalI, IlinaY, TamásMJ, WysockiR (2008) Mitogen-activated protein kinase Hog1 mediates adaptation to G1 checkpoint arrest during arsenite and hyperosmotic stress. Eukaryot Cell 7 : 1309–1317.

17. YenJL, SuNY, KaiserP (2005) The yeast ubiquitin ligase SCFMet30 regulates heavy metal response. Mol Biol Cell 16 : 1872–1882.

18. DildaPJ, PerroneGG, PhilpA, LockRB, DawesIW, et al. (2008) Insight into the selectivity of arsenic trioxide for acute promyelocytic leukemia cells by characterizing Saccharomyces cerevisiae deletion strains that are sensitive or resistant to the metalloid. Int J Biochem Cell Biol 40 : 1016–1029.

19. JoWJ, LoguinovA, WintzH, ChangM, SmithAH, et al. (2009) Comparative functional genomic analysis identifies distinct and overlapping sets of genes required for resistance to monomethylarsonous acid (MMAIII) and arsenite (AsIII) in yeast. Toxicol Sci 111 : 424–436.

20. ThorsenM, PerroneGG, KristianssonE, TrainiM, YeT, et al. (2009) Genetic basis of arsenite and cadmium tolerance in Saccharomyces cerevisiae. BMC Genomics 10 : 105.

21. PanX, ReissmanS, DouglasNR, HuangZ, YuanDS, et al. (2010) Trivalent arsenic inhibits the functions of chaperonin complex. Genetics 186 : 725–734.

22. ZhouX, AritaA, EllenTP, LiuX, BaiJ, et al. (2009) A genome-wide screen in Saccharomyces cerevisiae reveals pathways affected by arsenic toxicity. Genomics 94 : 294–307.

23. SanchezY, DesanyBA, JonesWJ, LiuQ, WangB, et al. (1996) Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle checkpoint pathways. Science 271 : 357–360.

24. SunZ, HsiaoJ, FayDS, SternDF (1998) Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint. Science 281 : 272–274.

25. PellicioliA, LuccaC, LiberiG, MariniF, LopesM, et al. (1999) Activation of Rad53 kinase in response to DNA damage and its effect in modulating phosphorylation of the lagging strand DNA polymerase. EMBO J 18 : 6561–6572.

26. RogakouEP, PilchDR, OrrAH, IvanovaVS, BonnerWM (1998) DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273 : 5858–5868.

27. DownsJA, LowndesNF, JacksonSP (2000) A role for Saccharomyces cerevisiae histone H2A in DNA repair. Nature 408 : 1001–1004.

28. WardIM, ChenJ (2001) Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem 276 : 47759–47762.

29. CobbJA, SchlekerT, RojasV, BjergbaekL, TerceroJA, et al. (2005) Replisome instability, fork collapse, and gross chromosomal rearrangements arise synergistically from Mec1 kinase and RecQ helicase mutations. Genes Dev 19 : 3055–3069.

30. Maciaszczyk-DziubinskaE, WawrzyckaD, WysockiR (2012) Arsenic and antimony transporters in eukaryotes. Int J Mol Sci 1 : 3527–3548.

31. FinnK, LowndesN, GrenonM (2012) Eukaryotic DNA damage checkpoint activation in response to double-strand breaks. Cell Mol Life Sci 69 : 1447–1473.

32. NakadaD, ShimomuraT, MatsumotoK, SugimotoK (2003) The ATM-related Tel1 protein of Saccharomyces cerevisiae controls a checkpoint response following phleomycin treatment. Nucleic Acids Res 31 : 1715–1724.

33. LeroyC, MannC, MarsolierMC (2001) Silent repair accounts for cell cycle specificity in the signaling of oxidative DNA lesions. EMBO J 20 : 2896–2906.

34. NikolovaT, EnsmingerM, LöbrichM, KainaB (2010) Homologous recombination protects mammalian cells from replication-associated DNA double-strand breaks arising in response to methyl methanesulfonate. DNA Repair (Amst) 9 : 1050–1063.

35. MoldovanGL, PfanderB, JentschS (2007) PCNA, the maestro of the replication fork. Cell 129 : 665–679.

36. UlrichHD (2009) Regulating post-translational modifications of the eukaryotic replication clamp PCNA. DNA Repair (Amst) 8 : 461–469.

37. DaviesAA, HuttnerD, DaigakuY, ChenS, UlrichHD (2008) Activation of ubiquitin-dependent DNA damage bypass is mediated by replication protein A. Mol Cell 29 : 625–636.

38. KroghBO, SymingtonLS (2004) Recombination proteins in yeast. Annu Rev Genet 38 : 233–271.

39. LisbyM, BarlowJH, BurgessRC, RothsteinR (2004) Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins. Cell 118 : 699–713.

40. CollinsAR (2004) The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol 26 : 249–261.

41. AzevedoF, MarquesF, FoktH, OliveiraR, JohanssonB (2011) Measuring oxidative DNA damage and DNA repair using the yeast comet assay. Yeast 28 : 55–61.

42. StanevaD, PeychevaE, GeorgievaM, EfremovT, MiloshevG (2013) Application of comet assay for the assessment of DNA damage caused by chemical genotoxins in the dairy yeast Kluyveromyces lactis. Antonie van Leeuwenhoek 103 : 143–152.

43. GeorgievaM, RoguevA, BalashevK, ZlatanovaJ, MiloshevG (2012) Hho1p, the linker histone of Saccharomyces cerevisiae, is important for the proper chromatin organization in vivo. Biochim Biophys Acta 1819 : 366–374.

44. MaW, ResnickMA, GordeninDA (2008) Apn1 and Apn2 endonucleases prevent accumulation of repair-associated DNA breaks in budding yeast as revealed by direct chromosomal analysis. Nucleic Acids Res 36 : 1836–1846.

45. BarlowJH, LisbyM, RothsteinR (2008) Differential regulation of the cellular response to DNA double-strand breaks in G1. Mol Cell 30 : 73–85.

46. BonettiD, ClericiM, ManfriniN, LucchiniG, LongheseMP, et al. (2010) The MRX complex plays multiple functions in resection of Yku -⁠ and Rif2-protected DNA ends. PLoS One 5: e14142.

47. SordetO, RedonCE, Guirouilh-BarbatJ, SmithS, SolierS, et al. (2009) Ataxia telangiectasia mutated activation by transcription -⁠ and topoisomerase I-induced DNA double-strand breaks. EMBO Rep 10 : 887–893.

48. DarouiP, DesaiSD, LiTK, LiuAA, LiuLF (2004) Hydrogen peroxide induces topoisomerase I-mediated DNA damage and cell death. J Biol Chem 279 : 14587–14594.

49. TipperDJ (1973) Inhibition of yeast ribonucleic acid polymerases by thiolutin. J Bacteriol 116 : 245–256.

50. GrigullJ, MnaimnehS, PootoolalJ, RobinsonMD, HughesTR (2004) Genome-wide analysis of mRNA stability using transcription inhibitors and microarrays reveals posttranscriptional control of ribosome biogenesis factors. Mol Cell Biol 24 : 5534–5547.

51. NonetM, ScafeC, SextonJ, YoungR (1987) Eukaryotic RNA polymerase conditional mutant that rapidly ceases mRNA synthesis. Mol Cell Biol 7 : 1602–1611.

52. JanKY, LinYC, HoIC, KaoSL, LeeTC (1990) Effects of sodium arsenite on the cytotoxicity of bleomycin. Toxicol Lett 51 : 81–90.

53. ChiuHW, LinJH, ChenYA, HoSY, WangYJ (2010) Combination treatment with arsenic trioxide and irradiation enhances cell-killing effects in human fibrosarcoma cells in vitro and in vivo through induction of both autophagy and apoptosis. Autophagy 6 : 353–365.

54. ChiuHW, ChenYA, HoSY, WangYJ (2012) Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells. PLoS One 7: e31579.

55. DiepartC, KarroumO, MagatJ, FeronO, VerraxJ, et al. (2012) Arsenic trioxide treatment decreases the oxygen consumption rate of tumor cells and radiosensitizes solid tumors. Cancer Res 72 : 482–490.

56. SternR, RoseJA, FriedmanRM (1974) Phleomycin-induced cleavage of deoxyribonucleic acid. Biochemistry 13 : 307–312.

57. RamotarD, WangH (2003) Protective mechanisms against the antitumor agent bleomycin: lessons from Saccharomyces cerevisiae. Curr Genet 43 : 213–224.

58. NikolovaT, EnsmingerM, LöbrichM, KainaB (2010) Homologous recombination protects mammalian cells from replication-associated DNA double-strand breaks arising in response to methyl methanesulfonate. DNA Repair (Amst) 9 : 1050–1063.

59. MaW, WestmorelandJW, GordeninDA, ResnickMA (2011) Alkylation base damage Is converted into repairable double-strand breaks and complex intermediates in G2 cells lacking AP endonuclease. PLoS Genet 7: e1002059.

60. GellonL, BarbeyR, Auffret van der KampP, ThomasD, BoiteuxS (2001) Synergism between base excision repair, mediated by DNA glycosylases Ntg1 and Ntg2, and nucleotide excision repair in removal of oxidatively damaged DNA bases in Saccharomyces cerevisiae. Mol Genet Genomics 265 : 1087–1096.

61. JohnsonRE, Torres-RamosCA, IzumiT, MitraS, PrakashS, et al. (1998) Identification of APN2, the Saccharomyces cerevisiae homolog of the major human AP endonuclease HAP1, and its role in the repair of abasic sites. Genes Dev 12 : 3137–3143.

62. XiaoW, ChowBL, HannaM, DoetschPW (2001) Deletion of the MAG1 DNA glycosylase gene suppresses alkylation-induced killing and mutagenesis in yeast cells lacing AP endocucleases. Mutat Res 487 : 137–147.

63. NafisiS, SobhanmaneshA, AlimoghaddamK, GhavamzadehA, Tajmir-RiahiHA (2005) Interaction of arsenic trioxide As2O3 with DNA and RNA. DNA Cell Biol 24 : 634–640.

64. MandalSM, GhoshAK, PatiBR, DasAK (2009) Detection of trivalent arsenic [As(III)] complex with DNA: a spectroscopic investigation. Toxicol Environ Chem 91 : 219–224.

65. KitchinKT, WallaceK (2008) Evidence against the nuclear in situ binding of arsenicals-oxidative stress theory of arsenic carcinogenesis. Toxicol Appl Pharmacol 232 : 252–257.

66. KehrerJP (2000) The Haber-Weiss reaction and mechanisms of toxicity. Toxicology 149 : 43–50.

67. AouidaM, RamotarD (2010) A new twist in cellular resistance to the anticancer drug bleomycin-A5. Curr Drug Metab 11 : 595–602.

68. LongtineMS, McKenzieA3rd, DemariniDJ, ShahNG, WachA, et al. (1998) Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 14 : 953–961.

69. WysockiR, JavaheriA, AllardS, ShaF, CôtéJ, et al. (2005) Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9. Mol Cell Biol 25 : 8430–8443.

70. WysockiR, KronSJ (2004) Yeast cell death during DNA damage arrest is independent of caspase or reactive oxygen species. J Cell Biol 166 : 311–316.