The ATR barrier to replication-born DNA damage

DNA Repair

Volumn 9, Issue 12, 2010, Pages 1249-1255

  López Contreras, Andrés J ^a   Fernandez Capetillo, Oscar ^a  

^a Centro Nacional de Investigaciones Oncológicas   (Spain)

Author keywords

Ageing; ATR; Cancer; Chk1; DNA damage response

Indexed keywords

ATM PROTEIN; CHECKPOINT KINASE 1; CHECKPOINT KINASE 2; PHOSPHATIDYLINOSITOL 3 KINASE; REACTIVE OXYGEN METABOLITE;

AMINO TERMINAL SEQUENCE; CELL AGING; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE S PHASE; CRANIOFACIAL MALFORMATION; DNA DAMAGE; DNA REPAIR; DNA REPLICATION; EXCISION REPAIR; HOMOLOGOUS RECOMBINATION; HUMAN; IONIZING RADIATION; LIFESPAN; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FAMILY; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; REVIEW; SECKEL SYNDROME; SENESCENCE; SUNLIGHT; UPREGULATION;

AGING; CELL CYCLE PROTEINS; DNA BREAKS, DOUBLE-STRANDED; DNA REPAIR; DNA REPLICATION; DNA, SINGLE-STRANDED; MODELS, BIOLOGICAL; NEOPLASMS; PHOSPHORYLATION; PROTEIN KINASES; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION;

MAMMALIA;

EID: 78649443528     PISSN: 15687864     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.dnarep.2010.09.012     Document Type: Review

References (91)

1. Jackson S.P., Bartek J. The DNA-damage response in human biology and disease. Nature 2009, 461:1071-1078.
2. Savitsky K., Bar-Shira A., Gilad S., Rotman G., Ziv Y., Vanagaite L., Tagle D.A., Smith S., Uziel T., Sfez S., Ashkenazi M., Pecker I., Frydman M., Harnik R., Patanjali S.R., Simmons A., Clines G.A., Sartiel A., Gatti R.A., Chessa L., Sanal O., Lavin M.F., Jaspers N.G., Taylor A.M., Arlett C.F., Miki T., Weissman S.M., Lovett M., Collins F.S., Shiloh Y. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 1995, 268:1749-1753.
3. Harper J.W., Elledge S.J. The DNA damage response: ten years after. Mol. Cell. 2007, 28:739-745.
4. Cimprich K.A., Cortez D. ATR: an essential regulator of genome integrity. Nat. Rev. Mol. Cell. Biol. 2008, 9:616-627.
5. Shiloh Y. ATM and related protein kinases: safeguarding genome integrity. Nat. Rev. Cancer 2003, 3:155-168.
6. Meek K., Dang V., Lees-Miller S.P. DNA-PK: the means to justify the ends?. Adv. Immunol. 2008, 99:33-58.
7. Callen E., Jankovic M., Wong N., Zha S., Chen H.T., Difilippantonio S., Di Virgilio M., Heidkamp G., Alt F.W., Nussenzweig A., Nussenzweig M. Essential role for DNA-PKcs in DNA double-strand break repair and apoptosis in ATM-deficient lymphocytes. Mol. Cell 2009, 34:285-297.
8. Stiff T., O'Driscoll M., Rief N., Iwabuchi K., Lobrich M., Jeggo P.A. ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer Res. 2004, 64:2390-2396.
9. Gurley K.E., Kemp C.J. Synthetic lethality between mutation in ATM and DNAPK(cs) during murine embryogenesis. Curr. Biol. 2001, 11:191-194.
10. Lovejoy C.A., Cortez D. Common mechanisms of PIKK regulation. DNA Repair (Amst.) 2009, 8:1004-1008.
11. Lavin M.F. Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat. Rev. Mol. Cell. Biol. 2008, 9:759-769.
12. Mordes D.A., Glick G.G., Zhao R., Cortez D. TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes Dev. 2008, 22:1478-1489.
13. Kumagai A., Lee J., Yoo H.Y., Dunphy W.G. TopBP1 activates the ATR-ATRIP complex. Cell 2006, 124:943-955.
14. Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R., 3rd K.E., Hurov J., Luo C.E., Bakalarski Z., Zhao N., Solimini Y., Lerenthal Y., Shiloh S.P., Gygi S.J., Elledge ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 2007, 316:1160-1166.
15. Chen Y., Poon R.Y. The multiple checkpoint functions of CHK1 and CHK2 in maintenance of genome stability. Front. Biosci. 2008, 13:5016-5029.
16. Cuadrado M., Martinez-Pastor B., Murga M., Toledo L.I., Gutierrez-Martinez P., Lopez E., Fernandez-Capetillo O. ATM regulates ATR chromatin loading in response to DNA double-strand breaks. J. Exp. Med. 2006, 203:297-303.
17. Jazayeri A., Falck J., Lukas C., Bartek J., Smith G.C., Lukas J., Jackson S.P. ATM-and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat. Cell Biol. 2006, 8:37-45.
18. Toledo L.I., Murga M., Gutierrez-Martinez P., Soria R., Fernandez-Capetillo O. ATR signaling can drive cells into senescence in the absence of DNA breaks. Genes Dev. 2008, 22:297-302.
19. Kumagai A., Dunphy W.G., Claspin a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts. Mol. Cell 2000, 6:839-849.
20. Paull T.T., Gellert M. The 3′ to 5′ exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks. Mol. Cell 1998, 1:969-979.
21. Nimonkar A.V., Ozsoy A.Z., Genschel J., Modrich P., Kowalczykowski S.C. Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:16906-16911.
22. Sartori A.A., Lukas C., Coates J., Mistrik M., Fu S., Bartek J., Baer R., Lukas J., Jackson S.P. Human CtIP promotes DNA end resection. Nature 2007, 450:509-514.
23. Zou L., Elledge S.J. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 2003, 300:1542-1548.
24. Garvik B., Carson M., Hartwell L. Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint. Mol Cell Biol. 1995, 15:6128-6138.
25. Lee S.E., Moore J.K., Holmes A., Umezu K., Kolodner R.D., Haber J.E. Saccharomyces Ku70, mre11/rad50 and RPA proteins regulate adaptation to G2/M arrest after DNA damage. Cell 1998, 94:399-409.
26. Cortez D., Guntuku S., Qin J., Elledge S.J. ATR and ATRIP: partners in checkpoint signaling. Science 2001, 294:1713-1716.
27. Byun T.S., Pacek M., Yee M.C., Walter J.C., Cimprich K.A. Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint. Genes Dev. 2005, 19:1040-1052.
28. Halazonetis T.D., Gorgoulis V.G., Bartek J. An oncogene-induced DNA damage model for cancer development. Science 2008, 319:1352-1355.
29. Branzei D., Foiani M. Maintaining genome stability at the replication fork. Nat. Rev. Mol. Cell. Biol. 2010, 11:208-219.
30. Yang X.H., Zou L. Recruitment of ATR-ATRIP, Rad17, and 9-1-1 complexes to DNA damage. Methods Enzymol. 2006, 409:118-131.
31. Lee J., Kumagai A., Dunphy W.G. The Rad9-Hus1-Rad1 checkpoint clamp regulates interaction of TopBP1 with ATR. J. Biol. Chem. 2007, 282:28036-28044.
32. Wang X., Zou L., Lu T., Bao S., Hurov K.E., Hittelman W.N., Elledge S.J., Li L. Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress. Mol. Cell 2006, 23:331-341.
33. Cimprich K.A., Shin T.B., Keith C.T., Schreiber S.L. cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein. Proc. Natl. Acad. Sci. U. S. A. 1996, 93:2850-2855.
34. Liu Q., Guntuku S., Cui X.S., Matsuoka S., Cortez D., Tamai K., Luo G., Carattini-Rivera S., DeMayo F., Bradley A., Donehower L.A., Elledge S.J. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev. 2000, 14:1448-1459.
35. Huertas P., Jackson S.P. Human CtIP mediates cell cycle control of DNA end resection and double strand break repair. J. Biol. Chem. 2009, 284:9558-9565.
36. Hirao A., Cheung A., Duncan G., Girard P.M., Elia A.J., Wakeham A., Okada H., Sarkissian T., Wong J.A., Sakai T., De Stanchina E., Bristow R.G., Suda T., Lowe S.W., Jeggo P.A., Elledge S.J., Mak T.W. Chk2 is a tumor suppressor that regulates apoptosis in both an ataxia telangiectasia mutated (ATM)-dependent and an ATM-independent manner. Mol Cell Biol. 2002, 22:6521-6532.
37. Takai H., Naka K., Okada Y., Watanabe M., Harada N., Saito S., Anderson C.W., Appella E., Nakanishi M., Suzuki H., Nagashima K., Sawa H., Ikeda K., Motoyama N. Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription. EMBO J. 2002, 21:5195-5205.
38. Fernandez-Capetillo O., Chen H.T., Celeste A., Ward I., Romanienko P.J., Morales J.C., Naka K., Xia Z., Camerini-Otero R.D., Motoyama N., Carpenter P.B., Bonner W.M., Chen J., Nussenzweig A. DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1. Nat. Cell Biol. 2002, 4:993-997.
39. Smits V.A., Reaper P.M., Jackson S.P. Rapid PIKK-dependent release of Chk1 from chromatin promotes the DNA-damage checkpoint response. Curr. Biol. 2006, 16:150-159.
40. Bartek J., Lukas J. Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 2003, 3:421-429.
41. Guardavaccaro D., Pagano M. Stabilizers and destabilizers controlling cell cycle oscillators. Mol. Cell 2006, 22:1-4.
42. Jin J., Shirogane T., Xu L., Nalepa G., Qin J., Elledge S.J., Harper J.W. SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase. Genes Dev. 2003, 17:3062-3074.
43. Xiao Z., Chen Z., Gunasekera A.H., Sowin T.J., Rosenberg S.H., Fesik S., Zhang H. Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents. J. Biol. Chem. 2003, 278:21767-21773.
44. Syljuasen R.G., Sorensen C.S., Hansen L.T., Fugger K., Lundin C., Johansson F., Helleday T., Sehested M., Lukas J., Bartek J. Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage. Mol Cell Biol. 2005, 25:3553-3562.
45. Beck H., Nahse V., Larsen M.S., Groth P., Clancy T., Lees M., Jorgensen M., Helleday T., Syljuasen R.G., Sorensen C.S. Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase. J. Cell Biol. 2010, 188:629-638.
46. Melixetian M., Klein D.K., Sorensen C.S., Helin K. NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint. Nat. Cell Biol. 2009, 11:1247-1253.
47. Taylor W.R., Stark G.R. Regulation of the G2/M transition by p53. Oncogene 2001, 20:1803-1815.
48. Bartkova J., Rezaei N., Liontos M., Karakaidos P., Kletsas D., Issaeva N., Vassiliou L.V., Kolettas E., Niforou K., Zoumpourlis V.C., Takaoka M., Nakagawa H., Tort F., Fugger K., Johansson F., Sehested M., Andersen C.L., Dyrskjot L., Orntoft T., Lukas J., Kittas C., Helleday T., Halazonetis T.D., Bartek J., Gorgoulis V.G. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 2006, 444:633-637.
49. Di Micco R., Fumagalli M., Cicalese A., Piccinin S., Gasparini P., Luise C., Schurra C., Garre M., Nuciforo P.G., Bensimon A., Maestro R., Pelicci P.G., d'Adda di Fagagna F. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 2006, 444:638-642.
50. Mallette F.A., Gaumont-Leclerc M.F., Ferbeyre G. The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence. Genes Dev. 2007, 21:43-48.
51. Tercero J.A., Diffley J.F. Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint. Nature 2001, 412:553-557.
52. Hanada K., Budzowska M., Davies S.L., van Drunen E., Onizawa H., Beverloo H.B., Maas A., Essers J., Hickson I.D., Kanaar R. The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks. Nat. Struct. Mol. Biol. 2007, 14:1096-1104.
53. Friedel A.M., Pike B.L., Gasser S.M. ATR/Mec1: coordinating fork stability and repair. Curr. Opin. Cell Biol. 2009, 21:237-244.
54. Brown E.J., Baltimore D. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev. 2000, 14:397-402.
55. de Klein A., Muijtjens M., van Os R., Verhoeven Y., Smit B., Carr A.M., Lehmann A.R., Hoeijmakers J.H. Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice. Curr. Biol. 2000, 10:479-482.
56. Takai H., Tominaga K., Motoyama N., Minamishima Y.A., Nagahama H., Tsukiyama T., Ikeda K., Nakayama K., Nakanishi M. Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice. Genes Dev. 2000, 14:1439-1447.
57. O'Driscoll M., Ruiz-Perez V.L., Woods C.G., Jeggo P.A., Goodship J.A. A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nat. Genet. 2003, 33:497-501.
58. Murga M., Bunting S., Montana M.F., Soria R., Mulero F., Canamero M., Lee Y., McKinnon P.J., Nussenzweig A., Fernandez-Capetillo O. A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging. Nat. Genet. 2009, 41:891-898.
59. Cobb J.A., Bjergbaek L., Shimada K., Frei C., Gasser S.M. DNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1. EMBO J. 2003, 22:4325-4336.
60. Lou H., Komata M., Katou Y., Guan Z., Reis C.C., Budd M., Shirahige K., Campbell J.L. Mrc1 and DNA polymerase epsilon function together in linking DNA replication and the S phase checkpoint. Mol. Cell 2008, 32:106-117.
61. Zhu Z., Chung W.H., Shim E.Y., Lee S.E., Ira G. Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends. Cell 2008, 134:981-994.
62. Davies S.L., North P.S., Hickson I.D. Role for BLM in replication-fork restart and suppression of origin firing after replicative stress. Nat. Struct. Mol. Biol. 2007, 14:677-679.
63. Pirzio L.M., Pichierri P., Bignami M., Franchitto A. Werner syndrome helicase activity is essential in maintaining fragile site stability. J. Cell Biol. 2008, 180:305-314.
64. Ge X.Q., Jackson D.A., Blow J.J. Dormant origins licensed by excess Mcm2-7 are required for human cells to survive replicative stress. Genes Dev. 2007, 21:3331-3341.
65. Shechter D., Costanzo V., Gautier J. ATR and ATM regulate the timing of DNA replication origin firing. Nat. Cell Biol. 2004, 6:648-655.
66. Wang H., Powell S.N., Iliakis G., Wang Y. ATR affecting cell radiosensitivity is dependent on homologous recombination repair but independent of nonhomologous end joining. Cancer Res. 2004, 64:7139-7143.
67. Foray N., Marot D., Gabriel A., Randrianarison V., Carr A.M., Perricaudet M., Ashworth A., Jeggo P. A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein. EMBO J. 2003, 22:2860-2871.
68. Tibbetts R.S., Cortez D., Brumbaugh K.M., Scully R., Livingston D., Elledge S.J., Abraham R.T. Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress. Genes Dev. 2000, 14:2989-3002.
69. Turner J.M., Aprelikova O., Xu X., Wang R., Kim S., Chandramouli G.V., Barrett J.C., Burgoyne P.S., Deng C.X. BRCA1, histone H2AX phosphorylation, and male meiotic sex chromosome inactivation. Curr. Biol. 2004, 14:2135-2142.
70. Sorensen C.S, Hansen L.T., Dziegielewski J., Syljuasen R.G., Lundin C., Bartek J., Helleday T. The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. Nat. Cell Biol. 2005, 7:195-201.
71. Andreassen P.R., D'Andrea A.D., Taniguchi T. ATR couples FANCD2 monoubiquitination to the DNA-damage response. Genes Dev. 2004, 18:1958-1963.
72. Collis S.J., Ciccia A., Deans A.J., Horejsi Z., Martin J.S., Maslen S.L., Skehel J.M., Elledge S.J., West S.C., Boulton S.J. FANCM, FAAP24 function in ATR-mediated checkpoint signaling independently of the Fanconi anemia core complex. Mol. Cell 2008, 32:313-324.
73. O'Driscoll M. Mouse models for ATR deficiency. DNA Repair (Amst.) 2009, 8:1333-1337.
74. Bartkova J., Horejsi Z., Koed K., Kramer A., Tort F., Zieger K., Guldberg P., Sehested M., Nesland J.M., Lukas C., Orntoft T., Lukas J., Bartek J. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 2005, 434:864-870.
75. Gorgoulis V.G., Vassiliou L.V., Karakaidos P., Zacharatos P., Kotsinas A., Liloglou T., Venere M., Ditullio R.A., Kastrinakis N.G., Levy B., Kletsas D., Yoneta A., Herlyn M., Kittas C., Halazonetis T.D. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 2005, 434:907-913.
76. Pusapati R.V., Rounbehler R.J., Hong S., Powers J.T., Yan M., Kiguchi K., McArthur M.J., Wong P.K., Johnson D.G. ATM promotes apoptosis and suppresses tumorigenesis in response to Myc. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:1446-1451.
77. Reimann M., Loddenkemper C., Rudolph C., Schildhauer I., Teichmann B., Stein H., Schlegelberger B., Dorken B., Schmitt C.A. The Myc-evoked DNA damage response accounts for treatment resistance in primary lymphomas in vivo. Blood 2007, 110:2996-3004.
78. Efeyan A., Murga M., Martinez-Pastor B., Ortega-Molina A., Soria R., Collado M., Fernandez-Capetillo O., Serrano M. Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression. PLoS One 2009, 4:e5475.
79. Fang Y., Tsao C.C., Goodman B.K., Furumai R., Tirado C.A., Abraham R.T., Wang X.F. ATR functions as a gene dosage-dependent tumor suppressor on a mismatch repair-deficient background. EMBO J. 2004, 23:3164-3174.
80. Lam M.H., Liu Q., Elledge S.J., Rosen J.M. Chk1 is haploinsufficient for multiple functions critical to tumor suppression. Cancer Cell 2004, 6:45-59.
81. Tao Z.F., Lin N.H. Chk1 inhibitors for novel cancer treatment. Anticancer Agents Med. Chem. 2006, 6:377-388.
82. Koniaras K., Cuddihy A.R., Christopoulos H., Hogg A., O'Connell M.J. Inhibition of Chk1-dependent G2 DNA damage checkpoint radiosensitizes p53 mutant human cells. Oncogene 2001, 20:7453-7463.
83. Ruzankina Y., Schoppy D.W., Asare A., Clark C.E., Vonderheide R.H., Brown E.J. Tissue regenerative delays and synthetic lethality in adult mice after combined deletion of Atr and Trp53. Nat. Genet. 2009, 41:1144-1149.
84. Heffernan T.P., Kawasumi M., Blasina A., Anderes K., Conney A.H., Nghiem P. ATR-Chk1 pathway inhibition promotes apoptosis after UV treatment in primary human keratinocytes: potential basis for the UV protective effects of caffeine. J. Invest. Dermatol. 2009, 129:1805-1815.
85. Kerzendorfer C., O'Driscoll M. UVB and caffeine: inhibiting the DNA damage response to protect against the adverse effects of UVB. J. Invest. Dermatol. 2009, 129:1611-1613.
86. Garinis G.A., van der Horst G.T., Vijg J., Hoeijmakers J.H. DNA damage and ageing: new-age ideas for an age-old problem. Nat. Cell Biol. 2008, 10:1241-1247.
87. Lombard D.B., Chua K.F., Mostoslavsky R., Franco S., Gostissa M., Alt F.W. DNA repair, genome stability, and aging. Cell 2005, 120:497-512.
88. Rossi D.J., Bryder D., Seita J., Nussenzweig A., Hoeijmakers J., Weissman I.L. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature 2007, 447:725-729.
89. Sedelnikova O.A., Horikawa I., Zimonjic D.B., Popescu N.C., Bonner W.M., Barrett J.C. Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Nat. Cell Biol. 2004, 6:168-170.
90. Ruzankina Y., Pinzon-Guzman C., Asare A., Ong T., Pontano L., Cotsarelis G., Zediak V.P., Velez M., Bhandoola A., Brown E.J. Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss. Cell Stem Cell 2007, 1:113-126.
91. Fernandez-Capetillo O. Intrauterine programming of ageing. EMBO Rep. 2010, 11:32-36.