Canonical Non-Homologous End Joining in Mitosis Induces Genome Instability and Is Suppressed by M-phase-Specific Phosphorylation of XRCC4

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DNA double-strand breaks (DSBs) are highly toxic to cells and often lead to genome instability and cell death. Organisms have several DSB repair mechanisms to prevent such instability. Proper choice of DSB repair pathways is highly regulated during the cell cycle. Inappropriate choice of the DSB repair pathway often results in perturbation or failure of DSB repair, which is occasionally associated with tumorigenesis. Although the DSB repair pathways in the cell-cycle phases G1, S, and G2 are well elucidated, little is known about how cells deal with DSBs induced during M phase. We found that M-phase DSBs trigger massive chromosome aberrations, suggesting a lack of and/or inappropriate DSB repair during M phase. Notably, DNA damage response factors do not localize to mitotic chromosomes, and DSB repair pathways seem to be largely suppressed during M phase. In this study, we show that the efficiency of DSB repair is low during mitosis rather than being completely repressed. DSB repair, which generally prevents genome instability, causes genome instability during M phase. Cells have a mechanism to suppress DSB repair during M phase to prevent genome instability by modifying a non-homologous end-joining factor that is critical for DSB repair during other cell-cycle phases.

Vyšlo v časopise: Canonical Non-Homologous End Joining in Mitosis Induces Genome Instability and Is Suppressed by M-phase-Specific Phosphorylation of XRCC4. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004563
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004563

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Zdroje

1. ChapmanJR, TaylorMR, BoultonSJ (2012) Playing the end game: DNA double-strand break repair pathway choice. Mol Cell 47: 497–510.

2. ShinoharaA, OgawaH, OgawaT (1992) Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell 69: 457–470.

3. BogueMA, WangC, ZhuC, RothDB (1997) V(D)J recombination in Ku86-deficient mice: distinct effects on coding, signal, and hybrid joint formation. Immunity 7: 37–47.

4. KabotyanskiEB, GomelskyL, HanJO, StamatoTD, RothDB (1998) Double-strand break repair in Ku86- and XRCC4-deficient cells. Nucleic Acids Res 26: 5333–5342.

5. LiangF, RomanienkoPJ, WeaverDT, JeggoPA, JasinM (1996) Chromosomal double-strand break repair in Ku80-deficient cells. Proc Natl Acad Sci U S A 93: 8929–8933.

6. McVeyM, LeeSE (2008) MMEJ repair of double-strand breaks (director's cut): deleted sequences and alternative endings. Trends Genet 24: 529–538.

7. ThompsonLH (2012) Recognition, signaling, and repair of DNA double-strand breaks produced by ionizing radiation in mammalian cells: the molecular choreography. Mutat Res 751: 158–246.

8. FalckJ, CoatesJ, JacksonSP (2005) Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 434: 605–611.

9. RogakouEP, BoonC, RedonC, BonnerWM (1999) Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 146: 905–916.

10. StuckiM, ClappertonJA, MohammadD, YaffeMB, SmerdonSJ, et al. (2005) MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123: 1213–1226.

11. DoilC, MailandN, Bekker-JensenS, MenardP, LarsenDH, et al. (2009) RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell 136: 435–446.

12. HuenMS, GrantR, MankeI, MinnK, YuX, et al. (2007) RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 131: 901–914.

13. KolasNK, ChapmanJR, NakadaS, YlankoJ, ChahwanR, et al. (2007) Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 318: 1637–1640.

14. MailandN, Bekker-JensenS, FaustrupH, MelanderF, BartekJ, et al. (2007) RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131: 887–900.

15. StewartGS, PanierS, TownsendK, Al-HakimAK, KolasNK, et al. (2009) The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Cell 136: 420–434.

16. BouwmanP, AlyA, EscandellJM, PieterseM, BartkovaJ, et al. (2010) 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat Struct Mol Biol 17: 688–695.

17. BuntingSF, CallenE, WongN, ChenHT, PolatoF, et al. (2010) 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141: 243–254.

18. LiuJ, DotyT, GibsonB, HeyerWD (2010) Human BRCA2 protein promotes RAD51 filament formation on RPA-covered single-stranded DNA. Nat Struct Mol Biol 17: 1260–1262.

19. SigurdssonS, TrujilloK, SongB, StrattonS, SungP (2001) Basis for avid homologous DNA strand exchange by human Rad51 and RPA. J Biol Chem 276: 8798–8806.

20. BishopDK, EarU, BhattacharyyaA, CalderoneC, BeckettM, et al. (1998) Xrcc3 is required for assembly of Rad51 complexes in vivo. J Biol Chem 273: 21482–21488.

21. VitaleI, GalluzziL, CastedoM, KroemerG (2011) Mitotic catastrophe: a mechanism for avoiding genomic instability. Nat Rev Mol Cell Biol 12: 385–392.

22. GiuntaS, BelotserkovskayaR, JacksonSP (2010) DNA damage signaling in response to double-strand breaks during mitosis. Journal of Cell Biology 190: 197–207.

23. ZhangW, PengG, LinSY, ZhangP (2011) DNA damage response is suppressed by the high cyclin-dependent kinase 1 activity in mitotic mammalian cells. J Biol Chem 286: 35899–35905.

24. OrthweinA, Fradet-TurcotteA, NoordermeerSM, CannyMD, BrunCM, et al. (2014) Mitosis inhibits DNA double-strand break repair to guard against telomere fusions. Science 344: 189–193.

25. LeeDH, AcharyaSS, KwonM, DraneP, GuanY, et al. (2014) Dephosphorylation Enables the Recruitment of 53BP1 to Double-Strand DNA Breaks. Mol Cell 54: 512–525.

26. AndreassenPR, LacroixFB, LohezOD, MargolisRL (2001) Neither p21WAF1 nor 14-3-3sigma prevents G2 progression to mitotic catastrophe in human colon carcinoma cells after DNA damage, but p21WAF1 induces stable G1 arrest in resulting tetraploid cells. Cancer Res 61: 7660–7668.

27. MikhailovA, ColeRW, RiederCL (2002) DNA damage during mitosis in human cells delays the metaphase/anaphase transition via the spindle-assembly checkpoint. Current Biology 12: 1797–1806.

28. SkoufiasDA, LacroixFB, AndreassenPR, WilsonL, MargolisRL (2004) Inhibition of DNA decatenation, but not DNA damage, arrests cells at metaphase. Mol Cell 15: 977–990.

29. MatsuzakiK, ShinoharaA, ShinoharaM (2008) Forkhead-associated domain of yeast Xrs2, a homolog of human Nbs1, promotes nonhomologous end joining through interaction with a ligase IV partner protein, Lif1. Genetics 179: 213–225.

30. MatsuzakiK, TerasawaM, IwasakiD, HigashideM, ShinoharaM (2012) Cyclin-dependent kinase-dependent phosphorylation of Lif1 and Sae2 controls imprecise nonhomologous end joining accompanied by double-strand break resection. Genes Cells 17: 473–493.

31. DaleyJM, PalmbosPL, WuD, WilsonTE (2005) Nonhomologous end joining in yeast. Annu Rev Genet 39: 431–451.

32. MaJL, KimEM, HaberJE, LeeSE (2003) Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences. Mol Cell Biol 23: 8820–8828.

33. MontgomeryE, WilentzRE, ArganiP, FisherC, HrubanRH, et al. (2003) Analysis of anaphase figures in routine histologic sections distinguishes chromosomally unstable from chromosomally stable malignancies. Cancer Biol Ther 2: 248–252.

34. ArtandiSE, ChangS, LeeSL, AlsonS, GottliebGJ, et al. (2000) Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature 406: 641–645.

35. AcilanC, PotterDM, SaundersWS (2007) DNA repair pathways involved in anaphase bridge formation. Genes, Chromosomes and Cancer 46: 522–531.

36. ChanKL, Palmai-PallagT, YingS, HicksonID (2009) Replication stress induces sister-chromatid bridging at fragile site loci in mitosis. Nat Cell Biol 11: 753–760.

37. van SteenselB, SmogorzewskaA, de LangeT (1998) TRF2 protects human telomeres from end-to-end fusions. Cell 92: 401–413.

38. HoffelderDR, LuoL, BurkeNA, WatkinsSC, GollinSM, et al. (2004) Resolution of anaphase bridges in cancer cells. Chromosoma 112: 389–397.

39. DaviesSL, BerghJ, HarrisAL, HicksonID (1997) Response to ICRF-159 in cell lines resistant to cleavable complex-forming topoisomerase II inhibitors. Br J Cancer 75: 816–821.

40. TanabeK, IkegamiY, IshidaR, AndohT (1991) Inhibition of topoisomerase II by antitumor agents bis(2,6-dioxopiperazine) derivatives. Cancer Res 51: 4903–4908.

41. GorbskyGJ (1994) Cell cycle progression and chromosome segregation in mammalian cells cultured in the presence of the topoisomerase II inhibitors ICRF-187 [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane; ADR-529] and ICRF-159 (Razoxane). Cancer Res 54: 1042–1048.

42. GoldbergIH (1987) Free radical mechanisms in neocarzinostatin-induced DNA damage. Free Radic Biol Med 3: 41–54.

43. HeydB, LeratG, AdjadjE, MinardP, DesmadrilM (2000) Reinvestigation of the proteolytic activity of neocarzinostatin. J Bacteriol 182: 1812–1818.

44. VenkitaramanAR (2002) Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 108: 171–182.

45. EliaAE, CantleyLC, YaffeMB (2003) Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates. Science 299: 1228–1231.

46. NakajimaH, Toyoshima-MorimotoF, TaniguchiE, NishidaE (2003) Identification of a consensus motif for Plk (Polo-like kinase) phosphorylation reveals Myt1 as a Plk1 substrate. J Biol Chem 278: 25277–25280.

47. AhnesorgP, SmithP, JacksonSP (2006) XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell 124: 301–313.

48. HammelM, ReyM, YuY, ManiRS, ClassenS, et al. (2011) XRCC4 protein interactions with XRCC4-like factor (XLF) create an extended grooved scaffold for DNA ligation and double strand break repair. J Biol Chem 286: 32638–32650.

49. PrzewlokaMR, PardingtonPE, YannoneSM, ChenDJ, CaryRB (2003) In vitro and in vivo interactions of DNA ligase IV with a subunit of the condensin complex. Molecular Biology of the Cell 14: 685–697.

50. SmogorzewskaA, KarlsederJ, Holtgreve-GrezH, JauchA, de LangeT (2002) DNA ligase IV-dependent NHEJ of deprotected mammalian telomeres in G1 and G2. Current Biology 12: 1635–1644.

51. LongheseMP (2008) DNA damage response at functional and dysfunctional telomeres. Genes Dev 22: 125–140.

52. NakadaS, KatsukiY, ImotoI, YokoyamaT, NagasawaM, et al. (2006) Early G2/M checkpoint failure as a molecular mechanism underlying etoposide-induced chromosomal aberrations. J Clin Invest 116: 80–89.

53. DawlatyMM, MalureanuL, JeganathanKB, KaoE, SustmannC, et al. (2008) Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha. Cell 133: 103–115.

54. SpenceJM, PhuaHH, MillsW, CarpenterAJ, PorterAC, et al. (2007) Depletion of topoisomerase IIalpha leads to shortening of the metaphase. Journal of Cell Science 120: 3952–3964.

55. MakharashviliN, TubbsAT, YangSH, WangH, BartonO, et al. (2014) Catalytic and Noncatalytic Roles of the CtIP Endonuclease in Double-Strand Break End Resection. Mol Cell 54: 1022–1033.

56. Zhang Y, Jasin M (2011) An essential role for CtIP in chromosomal translocation formation through an alternative end-joining pathway. Nat Struct Mol Biol. United States. pp. 80–84.

57. CelliGB, DenchiEL, de LangeT (2006) Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination. Nat Cell Biol 8: 885–890.

58. OlsenJV, VermeulenM, SantamariaA, KumarC, MillerML, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3: ra3.

59. LiF, MullinsJI (2002) Site-directed mutagenesis facilitated by DpnI selection on hemimethylated DNA. Methods Mol Biol 182: 19–27.

60. KimuraH, CookPR (2001) Kinetics of core histones in living human cells: little exchange of H3 and H4 and some rapid exchange of H2B. J Cell Biol 153: 1341–1353.

61. TerasawaM, ShinoharaA, HottaY, OgawaH, OgawaT (1995) Localization of RecA-like recombination proteins on chromosomes of the lily at various meiotic stages. Genes Dev 9: 925–934.

62. ShinoharaM, GasiorSL, BishopDK, ShinoharaA (2000) Tid1/Rdh54 promotes colocalization of rad51 and dmc1 during meiotic recombination. Proc Natl Acad Sci U S A 97: 10814–10819.

63. YuX, ChenJ (2004) DNA damage-induced cell cycle checkpoint control requires CtIP, a phosphorylation-dependent binding partner of BRCA1 C-terminal domains. Mol Cell Biol 24: 9478–9486.

64. RodrigueA, CoulombeY, JacquetK, GagneJP, RoquesC, et al. (2013) The RAD51 paralogs ensure cellular protection against mitotic defects and aneuploidy. J Cell Sci 126: 348–359.