Distinct but Concerted Roles of ATR, DNA-PK, and Chk1 in Countering Replication Stress during S Phase

Molecular Cell

Volumn 59, Issue 6, 2015, Pages 1011-1024

  Buisson, Rémi ^a   Boisvert, Jessica L ^a   Benes, Cyril H ^a   Zou, Lee ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATR PROTEIN; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; CHECKPOINT KINASE 1; CYCLIN E; DNA; DNA PK; HISTONE H2AX; MINICHROMOSOME MAINTENANCE PROTEIN 2; MINICHROMOSOME MAINTENANCE PROTEIN 7; PEVONEDISTAT; PROTEIN SERINE THREONINE KINASE INHIBITOR; ROSCOVITINE; SINGLE STRANDED DNA; UNCLASSIFIED DRUG; ATM PROTEIN; ATR PROTEIN, HUMAN; DNA DEPENDENT PROTEIN KINASE; NUCLEAR PROTEIN; PRKDC PROTEIN, HUMAN; PROTEIN KINASE; RIBONUCLEOSIDE DIPHOSPHATE REDUCTASE; RIBONUCLEOTIDE REDUCTASE M2;

ARTICLE; CANCER SURVIVAL; CELL CYCLE S PHASE; CELL DEATH; CELL SURVIVAL; CHROMATIN; CHROMOSOMAL INSTABILITY; COLORECTAL CANCER; COLORECTAL CANCER CELL LINE; CONTROLLED STUDY; CPG ISLAND; DNA CONTENT; DNA DAMAGE; DNA DAMAGE CHECKPOINT; DNA REPLICATION ORIGIN; ENZYME PHOSPHORYLATION; GENE SILENCING; HISTONE PHOSPHORYLATION; HUMAN; HUMAN CELL; MICROSATELLITE INSTABILITY; PROTEIN DEGRADATION; REDUCTION; TUNEL ASSAY; U2OS CELL LINE; UBIQUITINATION; DNA REPLICATION; GENETICS; METABOLISM; PHOSPHORYLATION; PHYSIOLOGICAL STRESS; PHYSIOLOGY; PROTEIN PROCESSING; TUMOR CELL LINE;

ATAXIA TELANGIECTASIA MUTATED PROTEINS; CELL LINE, TUMOR; DNA DAMAGE; DNA REPLICATION; DNA, SINGLE-STRANDED; DNA-ACTIVATED PROTEIN KINASE; HUMANS; NUCLEAR PROTEINS; PHOSPHORYLATION; PROTEIN KINASES; PROTEIN PROCESSING, POST-TRANSLATIONAL; REPLICATION ORIGIN; RIBONUCLEOSIDE DIPHOSPHATE REDUCTASE; S PHASE; STRESS, PHYSIOLOGICAL;

EID: 84941805396     PISSN: 10972765     EISSN: 10974164     Source Type: Journal    
DOI: 10.1016/j.molcel.2015.07.029     Document Type: Article

References (70)

1. Ahmed D., Eide P.W., Eilertsen I.A., Danielsen S.A., Eknæs M., Hektoen M., Lind G.E., Lothe R.A. Epigenetic and genetic features of 24 colon cancer cell lines. Oncogenesis 2013, 2:e71.
2. Bartkova J., Horejsí Z., Koed K., Krämer A., Tort F., Zieger K., Guldberg P., Sehested M., Nesland J.M., Lukas C., et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 2005, 434:864-870.
3. Bartkova J., Rezaei N., Liontos M., Karakaidos P., Kletsas D., Issaeva N., Vassiliou L.V., Kolettas E., Niforou K., Zoumpourlis V.C., et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 2006, 444:633-637.
4. Bastos de Oliveira F.M., Kim D., Cussiol J.R., Das J., Jeong M.C., Doerfler L., Schmidt K.H., Yu H., Smolka M.B. Phosphoproteomics reveals distinct modes of Mec1/ATR signaling during DNA replication. Mol. Cell 2015, 57:1124-1132.
5. Beck H., Nähse-Kumpf V., Larsen M.S., O'Hanlon K.A., Patzke S., Holmberg C., Mejlvang J., Groth A., Nielsen O., Syljuåsen R.G., Sørensen C.S. Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption. Mol. Cell. Biol. 2012, 32:4226-4236.
6. Brown E.J., Baltimore D. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev. 2000, 14:397-402.
7. Busino L., Donzelli M., Chiesa M., Guardavaccaro D., Ganoth D., Dorrello N.V., Hershko A., Pagano M., Draetta G.F. Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature 2003, 426:87-91.
8. Chabes A.L., Pfleger C.M., Kirschner M.W., Thelander L. Mouse ribonucleotide reductase R2 protein: a new target for anaphase-promoting complex-Cdh1-mediated proteolysis. Proc. Natl. Acad. Sci. USA 2003, 100:3925-3929.
9. Chanoux R.A., Yin B., Urtishak K.A., Asare A., Bassing C.H., Brown E.J. ATR and H2AX cooperate in maintaining genome stability under replication stress. J. Biol. Chem. 2009, 284:5994-6003.
10. Ciccia A., Elledge S.J. The DNA damage response: making it safe to play with knives. Mol. Cell 2010, 40:179-204.
11. Cimprich K.A., Cortez D. ATR: an essential regulator of genome integrity. Nat. Rev. Mol. Cell Biol. 2008, 9:616-627.
12. Cortez D., Guntuku S., Qin J., Elledge S.J. ATR and ATRIP: partners in checkpoint signaling. Science 2001, 294:1713-1716.
13. Costanzo V., Shechter D., Lupardus P.J., Cimprich K.A., Gottesman M., Gautier J. An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication. Mol. Cell 2003, 11:203-213.
14. Couch F.B., Bansbach C.E., Driscoll R., Luzwick J.W., Glick G.G., Bétous R., Carroll C.M., Jung S.Y., Qin J., Cimprich K.A., Cortez D. ATR phosphorylates SMARCAL1 to prevent replication fork collapse. Genes Dev. 2013, 27:1610-1623.
15. D'Angiolella V., Donato V., Forrester F.M., Jeong Y.T., Pellacani C., Kudo Y., Saraf A., Florens L., Washburn M.P., Pagano M. Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair. Cell 2012, 149:1023-1034.
16. DeGregori J., Kowalik T., Nevins J.R. Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes. Mol. Cell. Biol. 1995, 15:4215-4224.
17. Enoch T., Carr A.M., Nurse P. Fission yeast genes involved in coupling mitosis to completion of DNA replication. Genes Dev. 1992, 6:2035-2046.
18. Eykelenboom J.K., Harte E.C., Canavan L., Pastor-Peidro A., Calvo-Asensio I., Llorens-Agost M., Lowndes N.F. ATR activates the S-M checkpoint during unperturbed growth to ensure sufficient replication prior to mitotic onset. Cell Rep. 2013, 5:1095-1107.
19. Flynn R.L., Zou L. ATR: a master conductor of cellular responses to DNA replication stress. Trends Biochem. Sci. 2011, 36:133-140.
20. Flynn R.L., Cox K.E., Jeitany M., Wakimoto H., Bryll A.R., Ganem N.J., Bersani F., Pineda J.R., Suvà M.L., Benes C.H., et al. Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors. Science 2015, 347:273-277.
21. Foote K.M., Blades K., Cronin A., Fillery S., Guichard S.S., Hassall L., Hickson I., Jacq X., Jewsbury P.J., McGuire T.M., et al. Discovery of 4-4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-yl-1H-indole (AZ20): a potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity. J. Med. Chem. 2013, 56:2125-2138.
22. Forment J.V., Blasius M., Guerini I., Jackson S.P. Structure-specific DNA endonuclease Mus81/Eme1 generates DNA damage caused by Chk1 inactivation. PLoS ONE 2011, 6:e23517.
23. Garcia-Muse T., Boulton S.J. Distinct modes of ATR activation after replication stress and DNA double-strand breaks in Caenorhabditis elegans. EMBO J. 2005, 24:4345-4355.
24. Gilad O., Nabet B.Y., Ragland R.L., Schoppy D.W., Smith K.D., Durham A.C., Brown E.J. Combining ATR suppression with oncogenic Ras synergistically increases genomic instability, causing synthetic lethality or tumorigenesis in a dosage-dependent manner. Cancer Res. 2010, 70:9693-9702.
25. Gorgoulis V.G., Vassiliou L.V., Karakaidos P., Zacharatos P., Kotsinas A., Liloglou T., Venere M., Ditullio R.A., Kastrinakis N.G., Levy B., et al. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 2005, 434:907-913.
26. Heaphy C.M., Subhawong A.P., Hong S.M., Goggins M.G., Montgomery E.A., Gabrielson E., Netto G.J., Epstein J.I., Lotan T.L., Westra W.H., et al. Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes. Am. J. Pathol. 2011, 179:1608-1615.
27. Huang M., Elledge S.J. Identification of RNR4, encoding a second essential small subunit of ribonucleotide reductase in Saccharomyces cerevisiae. Mol. Cell. Biol. 1997, 17:6105-6113.
28. Hughes B.T., Sidorova J., Swanger J., Monnat R.J., Clurman B.E. Essential role for Cdk2 inhibitory phosphorylation during replication stress revealed by a human Cdk2 knockin mutation. Proc. Natl. Acad. Sci. USA 2013, 110:8954-8959.
29. 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.
30. Jossé R., Martin S.E., Guha R., Ormanoglu P., Pfister T.D., Reaper P.M., Barnes C.S., Jones J., Charlton P., Pollard J.R., et al. ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014, 74:6968-6979.
31. Karp J.E., Thomas B.M., Greer J.M., Sorge C., Gore S.D., Pratz K.W., Smith B.D., Flatten K.S., Peterson K., Schneider P., et al. Phase I and pharmacologic trial of cytosine arabinoside with the selective checkpoint 1 inhibitor Sch 900776 in refractory acute leukemias. Clin. Cancer Res. 2012, 18:6723-6731.
32. Kinzler K.W., Vogelstein B. Lessons from hereditary colorectal cancer. Cell 1996, 87:159-170.
33. Labib K. How do Cdc7 and cyclin-dependent kinases trigger the initiation of chromosome replication in eukaryotic cells?. Genes Dev. 2010, 24:1208-1219.
34. Laurençon A., Purdy A., Sekelsky J., Hawley R.S., Su T.T. Phenotypic analysis of separation-of-function alleles of MEI-41, Drosophila ATM/ATR. Genetics 2003, 164:589-601.
35. Lee Y., Shull E.R., Frappart P.O., Katyal S., Enriquez-Rios V., Zhao J., Russell H.R., Brown E.J., McKinnon P.J. ATR maintains select progenitors during nervous system development. EMBO J. 2012, 31:1177-1189.
36. Lin W.C., Lin F.T., Nevins J.R. Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation. Genes Dev. 2001, 15:1833-1844.
37. Liu Q., Guntuku S., Cui X.S., Matsuoka S., Cortez D., Tamai K., Luo G., Carattini-Rivera S., DeMayo F., Bradley A., et al. 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.
38. Lopez-Contreras A.J., Specks J., Barlow J.H., Ambrogio C., Desler C., Vikingsson S., Rodrigo-Perez S., Green H., Rasmussen L.J., Murga M., et al. Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice. Genes Dev. 2015, 29:690-695.
39. Ma C.X., Ellis M.J., Petroni G.R., Guo Z., Cai S.R., Ryan C.E., Craig Lockhart A., Naughton M.J., Pluard T.J., Brenin C.M., et al. A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer. Breast Cancer Res. Treat. 2013, 137:483-492.
40. Manning A.L., Yazinski S.A., Nicolay B., Bryll A., Zou L., Dyson N.J. Suppression of genome instability in pRB-deficient cells by enhancement of chromosome cohesion. Mol. Cell 2014, 53:993-1004.
41. Maréchal A., Zou L. DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb. Perspect. Biol. 2013, 5:a012716.
42. Maya-Mendoza A., Petermann E., Gillespie D.A., Caldecott K.W., Jackson D.A. Chk1 regulates the density of active replication origins during the vertebrate S phase. EMBO J. 2007, 26:2719-2731.
43. Murga M., Bunting S., Montaña M.F., Soria R., Mulero F., Cañamero 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.
44. Murga M., Campaner S., Lopez-Contreras A.J., Toledo L.I., Soria R., Montaña M.F., D'Artista L., Schleker T., Guerra C., Garcia E., et al. Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors. Nat. Struct. Mol. Biol. 2011, 18:1331-1335.
45. Neelsen K.J., Zanini I.M., Herrador R., Lopes M. Oncogenes induce genotoxic stress by mitotic processing of unusual replication intermediates. J. Cell Biol. 2013, 200:699-708.
46. Okita N., Minato S., Ohmi E., Tanuma S., Higami Y. DNA damage-induced CHK1 autophosphorylation at Ser296 is regulated by an intramolecular mechanism. FEBS Lett. 2012, 586:3974-3979.
47. Petermann E., Maya-Mendoza A., Zachos G., Gillespie D.A., Jackson D.A., Caldecott K.W. Chk1 requirement for high global rates of replication fork progression during normal vertebrate S phase. Mol. Cell. Biol. 2006, 26:3319-3326.
48. Petermann E., Helleday T., Caldecott K.W. Claspin promotes normal replication fork rates in human cells. Mol. Biol. Cell 2008, 19:2373-2378.
49. Petermann E., Woodcock M., Helleday T. Chk1 promotes replication fork progression by controlling replication initiation. Proc. Natl. Acad. Sci. USA 2010, 107:16090-16095.
50. Ragland R.L., Patel S., Rivard R.S., Smith K., Peters A.A., Bielinsky A.K., Brown E.J. RNF4 and PLK1 are required for replication fork collapse in ATR-deficient cells. Genes Dev. 2013, 27:2259-2273.
51. Randell J.C., Fan A., Chan C., Francis L.I., Heller R.C., Galani K., Bell S.P. Mec1 is one of multiple kinases that prime the Mcm2-7 helicase for phosphorylation by Cdc7. Mol. Cell 2010, 40:353-363.
52. Reaper P.M., Griffiths M.R., Long J.M., Charrier J.D., Maccormick S., Charlton P.A., Golec J.M., Pollard J.R. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat. Chem. Biol. 2011, 7:428-430.
53. Rhind N., Gilbert D.M. DNA replication timing. Cold Spring Harb. Perspect. Biol. 2013, 5:a010132.
54. 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.
55. Sano T., Asai A., Mishima K., Fujimaki T., Kirino T. Telomerase activity in 144 brain tumours. Br. J. Cancer 1998, 77:1633-1637.
56. Santocanale C., Sharma K., Diffley J.F. Activation of dormant origins of DNA replication in budding yeast. Genes Dev. 1999, 13:2360-2364.
57. Sausville E., Lorusso P., Carducci M., Carter J., Quinn M.F., Malburg L., Azad N., Cosgrove D., Knight R., Barker P., et al. Phase I dose-escalation study of AZD7762, a checkpoint kinase inhibitor, in combination with gemcitabine in US patients with advanced solid tumors. Cancer Chemother. Pharmacol. 2014, 73:539-549.
58. Schoppy D.W., Ragland R.L., Gilad O., Shastri N., Peters A.A., Murga M., Fernandez-Capetillo O., Diehl J.A., Brown E.J. Oncogenic stress sensitizes murine cancers to hypomorphic suppression of ATR. J. Clin. Invest. 2012, 122:241-252.
59. Seto T., Esaki T., Hirai F., Arita S., Nosaki K., Makiyama A., Kometani T., Fujimoto C., Hamatake M., Takeoka H., et al. Phase I, dose-escalation study of AZD7762 alone and in combination with gemcitabine in Japanese patients with advanced solid tumours. Cancer Chemother. Pharmacol. 2013, 72:619-627.
60. Shechter D., Costanzo V., Gautier J. ATR and ATM regulate the timing of DNA replication origin firing. Nat. Cell Biol. 2004, 6:648-655.
61. Soucy T.A., Smith P.G., Milhollen M.A., Berger A.J., Gavin J.M., Adhikari S., Brownell J.E., Burke K.E., Cardin D.P., Critchley S., et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 2009, 458:732-736.
62. Syljuåsen R.G., Sørensen 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.
63. Toledo L.I., Murga M., Zur R., Soria R., Rodriguez A., Martinez S., Oyarzabal J., Pastor J., Bischoff J.R., Fernandez-Capetillo O. A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations. Nat. Struct. Mol. Biol. 2011, 18:721-727.
64. Toledo L.I., Altmeyer M., Rask M.B., Lukas C., Larsen D.H., Povlsen L.K., Bekker-Jensen S., Mailand N., Bartek J., Lukas J. ATR prohibits replication catastrophe by preventing global exhaustion of RPA. Cell 2013, 155:1088-1103.
65. Vidal-Eychenié S., Décaillet C., Basbous J., Constantinou A. DNA structure-specific priming of ATR activation by DNA-PKcs. J. Cell Biol. 2013, 202:421-429.
66. Zeman M.K., Cimprich K.A. Causes and consequences of replication stress. Nat. Cell Biol. 2014, 16:2-9.
67. Zhang Y.W., Jones T.L., Martin S.E., Caplen N.J., Pommier Y. Implication of checkpoint kinase-dependent up-regulation of ribonucleotide reductase R2 in DNA damage response. J. Biol. Chem. 2009, 284:18085-18095.
68. Zhao H., Piwnica-Worms H. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol. Cell. Biol. 2001, 21:4129-4139.
69. Zhao X., Muller E.G., Rothstein R. A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools. Mol. Cell 1998, 2:329-340.
70. Zou L., Elledge S.J. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 2003, 300:1542-1548.