SV40 Utilizes ATM Kinase Activity to Prevent Non-homologous End Joining of Broken Viral DNA Replication Products

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Viruses from both Polyomaviridae and Papillomaviridae families share several characteristics. These include common modes of DNA replication and an accumulation of DNA damage signaling and repair proteins at replicating viral DNA. Several DNA repair proteins, with unknown functions during viral DNA replication, associate with the viral replication centers of the polyomavirus simian virus 40 (SV40). In this study we examined the mechanisms that regulate and recruit DNA repair machinery to replicating viral DNA during permissive SV40 infection. We found that the virus deploys DNA repair to broken viral DNA using cellular DNA damage signaling pathways. Our results shed light on why both Polyomaviridae and Papillomaviridae DNA replication elicits DNA damage signaling and repair. As no effective treatments currently exist for the Polyomaviridae family, our data identify pathways that might be therapeutically targeted to inhibit productive viral replication. Additionally, we categorize distinct functions for DNA repair and damage signaling pathways during viral replication. The results provide insights into how viruses exploit cellular processes to overwhelm the cell and propagate.

Vyšlo v časopise: SV40 Utilizes ATM Kinase Activity to Prevent Non-homologous End Joining of Broken Viral DNA Replication Products. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004536
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004536

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Zdroje

1. WagaS, StillmanB (1998) The DNA replication fork in eukaryotic cells. Annu Rev Biochem 67: 721–751.

2. MasaiH, MatsumotoS, YouZ, Yoshizawa-SugataN, OdaM (2010) Eukaryotic chromosome DNA replication: where, when, and how? Annu Rev Biochem 79: 89–130.

3. CicciaA, ElledgeSJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40: 179–204.

4. ZouL, ElledgeSJ (2003) Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300: 1542–1548.

5. GoodarziAA, JeggoPA (2013) The repair and signaling responses to DNA double-strand breaks. Adv Genet 82: 1–45.

6. NealJA, MeekK (2011) Choosing the right path: does DNA-PK help make the decision? Mutat Res 711: 73–86.

7. StrackerTH, PetriniJH (2011) The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol 12: 90–103.

8. SartoriAA, LukasC, CoatesJ, MistrikM, FuS, et al. (2007) Human CtIP promotes DNA end resection. Nature 450: 509–514.

9. HuertasP, JacksonSP (2009) Human CtIP mediates cell cycle control of DNA end resection and double strand break repair. J Biol Chem 284: 9558–9565.

10. NimonkarAV, GenschelJ, KinoshitaE, PolaczekP, CampbellJL, et al. (2011) BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev 25: 350–362.

11. PierceAJ, JohnsonRD, ThompsonLH, JasinM (1999) XRCC3 promotes homology-directed repair of DNA damage in mammalian cells. Genes Dev 13: 2633–2638.

12. MoynahanME, JasinM (2010) Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol 11: 196–207.

13. PetermannE, HelledayT (2010) Pathways of mammalian replication fork restart. Nat Rev Mol Cell Biol 11: 683–687.

14. DaviesSL, NorthPS, HicksonID (2007) Role for BLM in replication-fork restart and suppression of origin firing after replicative stress. Nat Struct Mol Biol 14: 677–679.

15. SchlacherK, ChristN, SiaudN, EgashiraA, WuH, et al. (2011) Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11. Cell 145: 529–542.

16. ChanKL, NorthPS, HicksonID (2007) BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges. EMBO J 26: 3397–3409.

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

18. LaulierC, ChengA, StarkJM (2011) The relative efficiency of homology-directed repair has distinct effects on proper anaphase chromosome separation. Nucleic Acids Res 39: 5935–5944.

19. FranchittoA, PichierriP (2011) Understanding the molecular basis of common fragile sites instability: role of the proteins involved in the recovery of stalled replication forks. Cell Cycle 10: 4039–4046.

20. HashimotoY, PudduF, CostanzoV (2012) RAD51- and MRE11-dependent reassembly of uncoupled CMG helicase complex at collapsed replication forks. Nat Struct Mol Biol 19: 17–24.

21. WechslerT, NewmanS, WestSC (2011) Aberrant chromosome morphology in human cells defective for Holliday junction resolution. Nature 471: 642–646.

22. AldertonGK, JoenjeH, VaronR, BorglumAD, JeggoPA, et al. (2004) Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway. Hum Mol Genet 13: 3127–3138.

23. CasperAM, DurkinSG, ArltMF, GloverTW (2004) Chromosomal instability at common fragile sites in Seckel syndrome. Am J Hum Genet 75: 654–660.

24. O'DriscollM, Ruiz-PerezVL, WoodsCG, JeggoPA, GoodshipJA (2003) A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nat Genet 33: 497–501.

25. QvistP, HuertasP, JimenoS, NyegaardM, HassanMJ, et al. (2011) CtIP Mutations Cause Seckel and Jawad Syndromes. PLoS Genet 7: e1002310.

26. ZhaoX, Madden-FuentesRJ, LouBX, PipasJM, GerhardtJ, et al. (2008) Ataxia telangiectasia-mutated damage-signaling kinase- and proteasome-dependent destruction of Mre11-Rad50-Nbs1 subunits in Simian virus 40-infected primate cells. J Virol 82: 5316–5328.

27. BoichukS, HuL, HeinJ, GjoerupOV (2010) Multiple DNA damage signaling and repair pathways deregulated by simian virus 40 large T antigen. J Virol 84: 8007–8020.

28. MoodyCA, LaiminsLA (2009) Human papillomaviruses activate the ATM DNA damage pathway for viral genome amplification upon differentiation. PLoS Pathog 5: e1000605.

29. GillespieKA, MehtaKP, LaiminsLA, MoodyCA (2012) Human papillomaviruses recruit cellular DNA repair and homologous recombination factors to viral replication centers. J Virol 86: 9520–9526.

30. SowdG, LiN, FanningE (2013) ATM and ATR Activities Maintain Replication Fork Integrity during SV40 Chromatin Replication. PLoS Pathog 9: e1003283.

31. OrbaY, SuzukiT, MakinoY, KubotaK, TanakaS, et al. (2010) Large T antigen promotes JC virus replication in G2-arrested cells by inducing ATM- and ATR-mediated G2 checkpoint signaling. J Biol Chem 285: 1544–1554.

32. JiangM, ZhaoL, GamezM, ImperialeMJ (2012) Roles of ATM and ATR-mediated DNA damage responses during lytic BK polyomavirus infection. PLoS Pathog 8: e1002898.

33. SakakibaraN, MitraR, McBrideAA (2011) The papillomavirus E1 helicase activates a cellular DNA damage response in viral replication foci. J Virol 85: 8981–8995.

34. SowdGA, FanningE (2012) A wolf in sheep's clothing: SV40 co-opts host genome maintenance proteins to replicate viral DNA. PLoS Pathog 8: e1002994.

35. ReaperPM, GriffithsMR, LongJM, CharrierJD, MaccormickS, et al. (2011) Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol 7: 428–430.

36. HicksonI, ZhaoY, RichardsonCJ, GreenSJ, MartinNM, et al. (2004) Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res 64: 9152–9159.

37. TapperDP, DePamphilisML (1978) Discontinuous DNA replication: accumulation of Simian virus 40 DNA at specific stages in its replication. J Mol Biol 120: 401–422.

38. GoffSP, BergP (1977) Structure and formation of circular dimers of simian virus 40 DNA. J Virol 24: 295–302.

39. SundinO, VarshavskyA (1980) Terminal stages of SV40 DNA replication proceed via multiply intertwined catenated dimers. Cell 21: 103–114.

40. PohlhausJR, KreuzerKN (2006) Formation and processing of stalled replication forks–utility of two-dimensional agarose gels. Methods Enzymol 409: 477–493.

41. Martin-ParrasL, LucasI, Martinez-RoblesML, HernandezP, KrimerDB, et al. (1998) Topological complexity of different populations of pBR322 as visualized by two-dimensional agarose gel electrophoresis. Nucleic Acids Res 26: 3424–3432.

42. VeugerSJ, CurtinNJ, RichardsonCJ, SmithGC, DurkaczBW (2003) Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and poly(ADP-ribose) polymerase-1. Cancer Res 63: 6008–6015.

43. WillmoreE, de CauxS, SunterNJ, TilbyMJ, JacksonGH, et al. (2004) A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia. Blood 103: 4659–4665.

44. MeekK, DouglasP, CuiX, DingQ, Lees-MillerSP (2007) trans Autophosphorylation at DNA-dependent protein kinase's two major autophosphorylation site clusters facilitates end processing but not end joining. Mol Cell Biol 27: 3881–3890.

45. NealJA, DangV, DouglasP, WoldMS, Lees-MillerSP, et al. (2011) Inhibition of homologous recombination by DNA-dependent protein kinase requires kinase activity, is titratable, and is modulated by autophosphorylation. Mol Cell Biol 31: 1719–1733.

46. ZhouY, PaullTT (2013) DNA-dependent protein kinase regulates DNA end resection in concert with Mre11-Rad50-Nbs1 (MRN) and ataxia telangiectasia-mutated (ATM). J Biol Chem 288: 37112–37125.

47. RigbyPW, BergP (1978) Does simian virus 40 DNA integrate into cellular DNA during productive infection? J Virol 28: 475–489.

48. SchirmbeckR, DeppertW (1987) Specific interaction of simian virus 40 large T antigen with cellular chromatin and nuclear matrix during the course of infection. J Virol 61: 3561–3569.

49. ChenBP, ChanDW, KobayashiJ, BurmaS, AsaithambyA, et al. (2005) Cell cycle dependence of DNA-dependent protein kinase phosphorylation in response to DNA double strand breaks. J Biol Chem 280: 14709–14715.

50. ChenBP, UematsuN, KobayashiJ, LerenthalY, KremplerA, et al. (2007) Ataxia telangiectasia mutated (ATM) is essential for DNA-PKcs phosphorylations at the Thr-2609 cluster upon DNA double strand break. J Biol Chem 282: 6582–6587.

51. UematsuN, WeteringsE, YanoK, Morotomi-YanoK, JakobB, et al. (2007) Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks. J Cell Biol 177: 219–229.

52. YajimaH, LeeKJ, ChenBP (2006) ATR-dependent phosphorylation of DNA-dependent protein kinase catalytic subunit in response to UV-induced replication stress. Mol Cell Biol 26: 7520–7528.

53. McKinnonPJ (2012) ATM and the molecular pathogenesis of ataxia telangiectasia. Annu Rev Pathol 7: 303–321.

54. LiaoH, WinkfeinRJ, MackG, RattnerJB, YenTJ (1995) CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis. J Cell Biol 130: 507–518.

55. ZhuX, ManciniMA, ChangKH, LiuCY, ChenCF, et al. (1995) Characterization of a novel 350-kilodalton nuclear phosphoprotein that is specifically involved in mitotic-phase progression. Mol Cell Biol 15: 5017–5029.

56. LobrichM, ShibataA, BeucherA, FisherA, EnsmingerM, et al. (2010) gammaH2AX foci analysis for monitoring DNA double-strand break repair: strengths, limitations and optimization. Cell Cycle 9: 662–669.

57. MatsuokaS, BallifBA, SmogorzewskaA, McDonaldER3rd, HurovKE, et al. (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316: 1160–1166.

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

59. WangH, ShiLZ, WongCC, HanX, HwangPY, et al. (2013) The interaction of CtIP and Nbs1 connects CDK and ATM to regulate HR-mediated double-strand break repair. PLoS Genet 9: e1003277.

60. TomimatsuN, MukherjeeB, BurmaS (2009) Distinct roles of ATR and DNA-PKcs in triggering DNA damage responses in ATM-deficient cells. EMBO Rep 10: 629–635.

61. RohalyG, KorfK, DehdeS, DornreiterI (2010) Simian virus 40 activates ATR-Delta p53 signaling to override cell cycle and DNA replication control. J Virol 84: 10727–10747.

62. JiangX, KlimovichV, ArunkumarAI, HysingerEB, WangY, et al. (2006) Structural mechanism of RPA loading on DNA during activation of a simple pre-replication complex. EMBO J 25: 5516–5526.

63. BrittonS, CoatesJ, JacksonSP (2013) A new method for high-resolution imaging of Ku foci to decipher mechanisms of DNA double-strand break repair. J Cell Biol 202: 579–595.

64. BeucherA, BirrauxJ, TchouandongL, BartonO, ShibataA, et al. (2009) ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2. EMBO J 28: 3413–3427.

65. TapperDP, AndersonS, DePamphilisML (1982) Distribution of replicating simian virus 40 DNA in intact cells and its maturation in isolated nuclei. J Virol 41: 877–892.

66. ShimadaK, PaseroP, GasserSM (2002) ORC and the intra-S-phase checkpoint: a threshold regulates Rad53p activation in S phase. Genes Dev 16: 3236–3252.

67. CobbJA, ShimadaK, GasserSM (2004) Redundancy, insult-specific sensors and thresholds: unlocking the S-phase checkpoint response. Curr Opin Genet Dev 14: 292–300.

68. BanerjeeP, DeJesusR, GjoerupO, SchaffhausenBS (2013) Viral interference with DNA repair by targeting of the single-stranded DNA binding protein RPA. PLoS Pathog 9: e1003725.

69. KousholtAN, FuggerK, HoffmannS, LarsenBD, MenzelT, et al. (2012) CtIP-dependent DNA resection is required for DNA damage checkpoint maintenance but not initiation. J Cell Biol 197: 869–876.

70. LobrichM, JeggoPA (2007) The impact of a negligent G2/M checkpoint on genomic instability and cancer induction. Nat Rev Cancer 7: 861–869.

71. BoutrosR, LobjoisV, DucommunB (2007) CDC25 phosphatases in cancer cells: key players? Good targets? Nat Rev Cancer 7: 495–507.

72. EricksonKD, Bouchet-MarquisC, HeiserK, Szomolanyi-TsudaE, MishraR, et al. (2012) Virion assembly factories in the nucleus of polyomavirus-infected cells. PLoS Pathog 8: e1002630.

73. TsangSH, WangX, LiJ, BuckCB, YouJ (2014) Host DNA damage response factors localize to merkel cell polyomavirus DNA replication sites to support efficient viral DNA replication. J Virol 88: 3285–3297.

74. DarbinyanA, WhiteMK, AkanS, RadhakrishnanS, Del ValleL, et al. (2007) Alterations of DNA damage repair pathways resulting from JCV infection. Virology 364: 73–86.

75. ShibataA, ConradS, BirrauxJ, GeutingV, BartonO, et al. (2011) Factors determining DNA double-strand break repair pathway choice in G2 phase. EMBO J 30: 1079–1092.

76. YunMH, HiomK (2009) CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle. Nature 459: 460–463.

77. RassE, ChandramoulyG, ZhaS, AltFW, XieA (2013) Ataxia telangiectasia mutated (ATM) is dispensable for endonuclease I-SceI-induced homologous recombination in mouse embryonic stem cells. J Biol Chem 288: 7086–7095.

78. BerkovichE, MonnatRJJr, KastanMB (2007) Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair. Nat Cell Biol 9: 683–690.

79. ShibataA, MoianiD, ArvaiAS, PerryJ, HardingSM, et al. (2014) DNA double-strand break repair pathway choice is directed by distinct MRE11 nuclease activities. Mol Cell 53: 7–18.

80. BoldersonE, TomimatsuN, RichardDJ, BoucherD, KumarR, et al. (2010) Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks. Nucleic Acids Res 38: 1821–1831.

81. AbabouM, DutertreS, LecluseY, OnclercqR, ChattonB, et al. (2000) ATM-dependent phosphorylation and accumulation of endogenous BLM protein in response to ionizing radiation. Oncogene 19: 5955–5963.

82. SinghTR, AliAM, BusyginaV, RaynardS, FanQ, et al. (2008) BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome. Genes Dev 22: 2856–2868.

83. PootRA, BozhenokL, van den BergDL, SteffensenS, FerreiraF, et al. (2004) The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci. Nat Cell Biol 6: 1236–1244.

84. DeppertW, GurneyEG, HarrisonRO (1981) Monoclonal antibodies against simian virus 40 tumor antigens: analysis of antigenic binding sites, using adenovirus type 2-simian virus 40 hybrid viruses. J Virol 37: 478–482.

85. MenearKA, AdcockC, BoulterR, CockcroftXL, CopseyL, et al. (2008) 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin- 1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J Med Chem 51: 6581–6591.

86. LucasI, GermeT, Chevrier-MillerM, HyrienO (2001) Topoisomerase II can unlink replicating DNA by precatenane removal. EMBO J 20: 6509–6519.