Cell-free Xenopus egg extracts for studying DNA damage response pathways

International Journal of Developmental Biology

Volumn 60, Issue 7-9, 2016, Pages 229-236

  Cupello, Steven ^a   Richardson, Christine ^a   Yan, Shan ^a  

^a UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE   (United States)

Author keywords

ATM Chk2; ATR Chk1; DNA damage response; TLS; Xenopus egg extracts

Indexed keywords

ATR PROTEIN; CHECKPOINT KINASE 1; DNA POLYMERASE; DNA POLYMERASE KAPPA; DNA POLYMERASE REV1; UNCLASSIFIED DRUG;

ARTICLE; CELL FREE SYSTEM; DNA CROSS LINKING; DNA DAMAGE; DNA REPLICATION; DNA SYNTHESIS; DOUBLE STRANDED DNA BREAK; EGG EXTRACT; ENZYME ACTIVATION; ENZYME INHIBITION; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; XENOPUS LAEVIS; ANIMAL; APOPTOSIS; CELL AGING; METABOLISM; OOCYTE; PHYSIOLOGY; XENOPUS;

ANIMALS; APOPTOSIS; CELL-FREE SYSTEM; CELLULAR SENESCENCE; DNA DAMAGE; OOCYTES; XENOPUS;

EID: 84991571364     PISSN: 02146282     EISSN: None     Source Type: Journal    
DOI: 10.1387/ijdb.160113sy     Document Type: Article

References (103)

1. ANTONI, L., SODHA, N., COLLINS, I. and GARRETT, M.D. (2007). CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin? Nat Rev Cancer 7: 925-936.
2. BAI, L., MICHAEL, W.M. and YAN, S. (2014). Importin beta-dependent nuclear import of TopBP1 inATR-Chk1 checkpoint in Xenopus egg extracts. Cell Signal 26: 857-867.
3. BAKKENIST, C.J. and KASTAN, M.B. (2003). DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421: 499-506.
4. BARTKOVA, J., HOREJSÍ, Z., KOED, K., KRÄMER, A., TORT, F., ZIEGER, K., GULD-BERG, P., SEHESTED, M., NESLAND, J., LUKAS, C., ORNTOFT, T., LUKAS, J. and BARTEK, J. (2005). DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434: 864-870.
5. BEN-YEHOYADA, M., WANG, L.C., KOZEKOV, I.D., RIZZO, C.J., GOTTESMAN, M.E. and GAUTIER, J. (2009). Checkpoint signaling from a single DNA interstrand crosslink. Mol Cell 35: 704-715.
6. BERQUIST, B.R. and WILSON, D.M. (2012). Pathways for repairing and tolerating the spectrum of oxidative DNA lesions. Cancer Lett 327: 61-72.
7. BETOUS, R., PILLAIRE, M.J., PIERINI, L., VAN DER LAAN, S., RECOLIN, B., OHL-SEGUY, E., GUO, C., NIIMI, N., GRUZ, P., NOHMI, T., FRIEDBERG, E., CAZAUX, C., MAIORANO, D. and J.S. HOFFMANN. (2013). DNA polymerase kappa-dependent DNA synthesis at stalled replication forks is important for CHK1 activation. EMBO J 32: 2172-85.
8. BLOW, J.J., DILWORTH, S.M., DINGWALL, C., MILLS, A.D. and LASKEY, R.A. (1987). Chromosome replication in cell-free systems from Xenopus eggs. Philos Trans R Soc Lond B Biol Sci 317: 483-494.
9. BLOW, J.J. and Laskey, R.A. (1986). Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of Xenopus eggs. Cell 47: 577-587.
10. BOUWMAN, P. and JONKERS, J. (2012). The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance. Nat Rev Cancer 12: 587-598.
11. BRANZEI, D. and FOIANI, M. (2010). Maintaining genome stability at the replication fork. Nat Rev Mol Cell Biol 11: 208-219.
12. BYUN, T.S., PACEK, M., YEE, M.C., WALTER, J.C. and CIMPRICH, K.A. (2005). Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint. Genes Dev 19: 1040-1052.
13. CADET, J., RAVANAT, J.L., TAVERNAPORRO, M., MENONI, H. and ANGELOV, D. (2012). Oxidatively generated complex DNA damage: tandem and clustered lesions. Cancer Lett 327: 5-15.
14. CHANG, D.J. and CIMPRICH, K.A. (2009). DNA damage tolerance: when it’s OK to make mistakes. Nat Chem Biol 5: 82-90.
15. CHARAMES, G.S. and BAPAT, B. (2003). Genomic instability and cancer. Curr Mol Med 3: 589-596.
16. CHEN, Y. and SANCHEZ, Y. (2004). Chk1 in the DNA damage response: conserved roles from yeasts to mammals. DNA Repair (Amst) 3: 1025-1032.
17. CICCIA, A. and ELLEDGE, S.J. (2010). The DNA damage response: making it safe to play with knives. Mol Cell 40: 179-204.
18. CIMPRICH, K.A. and CORTEZ, D. (2008). ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 9: 616-627.
19. COSTANZO, V. and GAUTIER, J. (2004). Xenopus cell-free extracts to study DNA damage checkpoints. Methods Mol Biol 241: 255-267.
20. COSTANZO, V., ROBERTSON, K., YING, C.Y., KIM, E., AVVEDIMENTO, E., GOT-TESMAN, M., GRIECO, D. and GAUTIER, J. (2000). Reconstitution of an ATM-dependent checkpoint that inhibits chromosomal DNA replication following DNA damage. Mol Cell 6: 649-659.
21. COSTANZO, V., SHECHTER, D., LUPARDUS, P.J., CIMPRICH, K.A., GOTTESMAN, M. and GAUTIER, J. (2003). An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication. Mol Cell 11: 203-213.
22. CURTIN, N.J. (2012). DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer. 12: 801-817.
23. DANIEL, J.A., PELLEGRINI, M., LEE, B.S., GUO, Z., FILSUF, D., BELKINA, N.V., YOU, Z., PAULL, T.T., SLECKMAN, B.P., FEIGENBAUM, L. and NUSSENZWEIG, A. (2012). Loss of ATM kinase activity leads to embryonic lethality in mice. J Cell Biol 198: 295-304.
24. DELACROIX, S., WAGNER, J.M., KOBAYASHI, M., YAMAMOTO, K. and KARNITZ, L.M. (2007). The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1. Genes Dev 21: 1472-1477.
25. DESTEPHANIS, D., MCLEOD, M. and YAN, S. (2015). REV1 is important for the ATR-Chk1 DNA damage response pathway in Xenopus egg extracts. Biochem Biophys Res Commun 460: 609-615.
26. DIZDAROGLU, M. (2012). Oxidatively induced DNA damage: mechanisms, repair and disease. Cancer Lett 327: 26-47.
27. DUURSMA, A.M., DRISCOLL, R., ELIAS, J.E. and CIMPRICH, K.A. (2013). A role for the MRN complex inATR activation via TOPBP1 recruitment. Mol Cell 50: 116-122.
28. FOKAS, E., PREVO, R., HAMMOND, E.M., T.B. BRUNNER, MCKENNA, W.G., and MUSCHEL, R.J. (2014). Targeting ATR in DNA damage response and cancer therapeutics. Cancer Treat Rev 40: 109-117.
29. FOKAS, E., PREVO, R., POLLARD, J.R., REAPER, P.M., CHARLTON, P.A., CORNE-LISSEN, B., VALLIS, K.A., HAMMOND, E.M., OLCINA, M.M., GILLIES MCKENNA, W., MUSCHEL, R.J. and BRUNNER, T.B. (2012). Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis 3:e441.
30. GANDINI ATTARDI, D., MARTINI, G., MATTOCCIA, E. and TOCCHINI-VALENTINI, G.P. (1976). Effect of Xenopus laevis oocyte extract on supercoiled simian virus 40 DNA: formation of complex DNA. Proc Natl Acad Sci USA 73: 554-558.
31. GUO, Z., KOZLOV, S., LAVIN, M.F., PERSON, M.D. and PAULL, T.T. (2010). ATM activation by oxidative stress. Science 330: 517-521.
32. GUO, Z., KUMAGAI, A., WANG, S.X. and DUNPHY, W.G. (2000). Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation in response to DNA replication blocks and UV-damaged DNA in Xenopus egg extracts. Genes Dev 14: 2745-2756.
33. HANAHAN, D. and WEINBERG, R.A. (2011). Hallmarks of cancer: the next generation. Cell 144: 646-674.
34. HARRISON, J.C., and Haber, J.E. (2006). Surviving the breakup: the DNA damage checkpoint. Annu Rev Genet 40: 209-235.
35. HO, T.V. and SCHARER, O.D. (2010). Translesion DNA synthesis polymerases in DNA interstrand crosslink repair. Environ Mol Mutagen 51: 552-566.
36. HOSOYA, N., and MIYAGAWA, K. (2014). Targeting DNA damage response in cancer therapy. Cancer Sci 105: 370-388.
37. JACKSON, S.P. and BARTEK, J. (2009). The DNA-damage response in human biology and disease. Nature 461: 1071-1078.
38. JAZAYERI, A., BALESTRINI, A., GARNER, E., HABER, J.E. and COSTANZO, V. (2008). Mre11-Rad50-Nbs1-dependent processing of DNA breaks generates oligonucleotides that stimulate ATM activity. EMBO J 27: 1953-1962.
39. JONES, D.P. 2006. Redefining oxidative stress. Antioxid Redox Signal. 8: 1865-1879.
40. KARPINKA, J.B., FORTRIEDE, J.D., BURNS, K.A., JAMES-ZORN, C., PONFER-RADA, V.G., LEE, J., KARIMI, K., ZORN, A.M. and VIZE, P.D. (2015). Xenbase, the Xenopus model organism database; new virtualized system, data types and genomes. Nucleic Acids Res 43:D756-763.
41. KASTAN, M.S. and BARTEK, J. (2004). Cell-cycle checkpoints and cancer. Nature 432: 316-323.
42. KHORONENKOVA, S.V. and DIANOV, G.L. (2015). ATM prevents DSB formation by coordinating SSB repair and cell cycle progression. Proc Natl Acad Sci USA 112: 3997-4002.
43. KNIPSCHEER, P., RASCHLE, M., SMOGORZEWSKA, A., ENOIU, M., HO, T.V., SCHARER, O.D., ELLEDGE, S.J. and WALTER, J.C. (2009). The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair. Science 326: 1698-1701.
44. KOUSHOLT, A.N., FUGGER, K., HOFFMANN, S., LARSEN, B.D., MENZEL, T., SARTORI, A.A. and SORENSEN, C.S. (2012). CtIP-dependent DNA resection is required for DNA damage checkpoint maintenance but not initiation. J Cell Biol 197: 869-876.
45. KUMAGAI, A., and DUNPHY, W.G. (2000). Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts. Mol Cell 6: 839-849.
46. KUMAGAI, A., LEE, J., YOO, H.Y. and DUNPHY, W.G. (2006). TopBP1 activates the ATR-ATRIP complex. Cell 124: 943-955.
47. LASKEY, R.A., MILLS, A.D. and MORRIS, N.R. (1977). Assembly of SV40 chromatin in a cell-free system from Xenopus eggs. Cell 10: 237-243.
48. LAVIN, M.F. (2008). Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol 9: 759-769.
49. LAVIN, M.F., KOZLOV, S., GATEI, M. and KIJAS, A.W. (2015). ATM-Dependent Phosphorylation of All Three Members of the MRN Complex: From Sensor to Adaptor. Biomolecules 5: 2877-2902.
50. LEBOFSKY, R., TAKAHASHI, T. and WALTER, J.C. (2009). DNA replication in nucleus-free Xenopus egg extracts. Methods Mol Biol 521: 229-252.
51. LEE, J.H. and PAULL, T.T. (2005). ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 308: 551-554.
52. LINDAHL, T. 1993. Instability and decay of the primary structure of DNA. Nature 362: 709-715.
53. LIU, S., SHIOTANI, B., LAHIRI, M., MARECHAL, A., TSE, A., LEUNG, C.C., GLOVER, J.N., YANG, X.H. and ZOU, L. (2011). ATR autophosphorylation as a molecular switch for checkpoint activation. Mol Cell 43: 192-202.
54. LONG, D.T. and WALTER, J.C. (2012). A novel function for BRCA1 in crosslink repair. Mol Cell 46: 111-112.
55. LOPES, M., FOIANI, M. and SOGO, J.M. (2006). Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions. Mol Cell 21: 15-27.
56. LUPARDUS, P.J., BYUN, T., YEE, M.C., HEKMAT-NEJAD, M. and CIMPRICH, K.A. (2002). A requirement for replication in activation of the ATR-dependent DNA damage checkpoint. Genes Dev 16: 2327-2332.
57. MACDOUGALL, C.A., BYUN, T.S., VAN, C., YEE, M.C. and CIMPRICH, K.A. (2007). The structural determinants of checkpoint activation. Genes Dev 21: 898-903.
58. MACHERET, M. and HALAZONETIS, T.D. (2015). DNA replication stress as a hallmark of cancer. Annu Rev Pathol 10: 425-448.
59. MARTEIL, G., GAGNÉ, J.P., BORSUK, E., RICHARD-PARPAILLON, L., POIRIER, G.G., and KUBIAK, J.Z. (2012). Proteomics reveals a switch in CDK1-associated proteins upon M-phase exit during the Xenopus laevis oocyte to embryo transition. Int J Biochem Cell Biol 44: 53-64.
60. MATSUOKA, S., BALLIF, B.A., SMOGORZEWSKA, A., MCDONALD, 3rd, E.R., HUROV, K.E., LUO, J., BAKALARSKI, C.E., ZHAO, Z., SOLIMINI, N., LERENTHAL, Y., SHILOH, Y., GYGI, S.P. and ELLEDGE, S.J. (2007). ATM and ATR substrate analysis reveals extensive protein networks responsive to DNAdamage. Science 316: 1160-1166.
61. MAZOUZI, A., VELIMEZI, G. and LOIZOU, J.I. (2014). DNA replication stress: causes, resolution and disease. Exp Cell Res 329: 85-93.
62. MCVEY, M. 2010. Strategies for DNA interstrand crosslink repair: insights from worms, flies, frogs, and slime molds. Environ Mol Mutagen 51: 646-658.
63. MICHAEL, W.M., OTT, J., FANNING, E. and NEWPORT, J. (2000). Activation of the DNA Replication Checkpoint Through RNA Synthesis by Primase. Science 289: 2133-2137.
64. NAKAYAMA, T., FISH, M.B., FISHER, M., OOMEN-HAJAGOS, J., THOMSEN, G.H. and GRAINGER, R.M. (2013). Simple and efficient CRISPR/Cas9-mediated targeted mutagenesis in Xenopus tropicalis. Genesis 51: 835-843.
65. O’DONNELL, M., LANGSTON, L. and STILLMAN, B. (2013). Principles and concepts of DNA replication in bacteria, archaea, and eukarya. Cold Spring Harb Perspect Biol 5: a010108.
66. NEWPORT, J. (1987). Nuclear reconstitution In vitro: stages of assembly around protein-free DNA. Cell 48: 205-217.
67. PAULL, T.T. (2015). Mechanisms of ATM Activation. Annu Rev Biochem 84: 711-738.
68. PHILPOTT, A. and YEW, P.R. (2008). The Xenopus cell cycle: an overview. Mol Biotechnol 39: 9-19.
69. RAMIREZ-LUGO, J.S., YOO, H.Y., YOON, S.J. and DUNPHY, W.G. (2011). CtIP interacts with TopBP1 and Nbs1 in the response to double-stranded DNA breaks (DSBs) in Xenopus egg extracts. Cell Cycle 10: 469-480.
70. RASCHLE, M., KNIPSCHEER, P., ENOIU, M., ANGELOV, T., SUN, J., GRIFFITH, J.D., ELLENBERGER, T.E., SCHARER, O.D. and WALTER, J.C. (2008). Mechanism of replication-coupled DNA interstrand crosslink repair. Cell 134: 969-980.
71. RASCHLE, M., SMEENK, G., HANSEN, R.K., TEMU, T., OKA, Y., HEIN, M.Y., NAGARAJ, N., LONG, D.T., WALTER, J.C., HOFMANN, K., STORCHOVA, Z., COX, J., BEKKER-JENSEN, S., MAILAND, N. and MANN, M. (2015). Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links. Science 348: 1253671.
72. RICHARDSON, C., YAN, S. and VESTAL, C.G. (2015). Oxidative Stress, Bone Marrow Failure, and Genome Instability in Hematopoietic Stem Cells. Int J Mol Sci 16: 2366-2385.
73. RILEY, P.A. (1994). Free radicals in biology: oxidative stress and the effects of ionizing radiation. Inter J Radiat Biol 65: 27-33.
74. ROTMAN, G. and SHILOH, Y. (1999). ATM: a mediator of multiple responses to genotoxic stress. Oncogene 18: 6135-6144.
75. SARTORI, A.A., LUKAS, C., COATES, J., MISTRIK, M., FU, S., BARTEK, J., BAER, R., LUKAS, J. and JACKSON, S.P. (2007). Human CtIP promotes DNA end resection. Nature 450: 509-514.
76. SCHEKMAN, R., A. WEINER, AND A. KORNBERG. 1974. Multienzyme systems of DNA replication. Science 186: 987-993.
77. SHI, Z., WANG, F., CUI, Y., LIU, Z., GUO, X., ZHANG, Y., DENG, Y., ZHAO, H., and CHEN, Y. (2015). Heritable CRISPR/Cas9-mediated targeted integration in Xenopus tropicalis. FASEB J. 29: 4914-4923.
78. SHIOTANI, B. and ZOU, L. (2009). Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks. Mol Cell 33: 547-558.
79. SIES, H. (1997). Oxidative stress: oxidants and antioxidants. Exp Physiol 82: 291-295.
80. SMITH, J., THO, L.M., XU, N. and GILLESPIE, D.A. (2010). The ATM-Chk2 and ATR-Chk1 pathways in DNAdamage signaling and cancer. Adv Cancer Res 108: 73-112.
81. TOLEDO, L.I., MURGA, M. and FERNANDEZ-CAPETILLO, O. (2011). Targeting ATR and Chk1 kinases for cancer treatment: a new model for new (and old) drugs. Mol Oncol 5: 368-373.
82. TRENZ, K., ERRICO, A. and COSTANZO, V. (2008). Plx1 is required for chromosomal DNA replication under stressful conditions. EMBO J 27: 876-885.
83. TRENZ, K., SMITH, E., SMITH, S. andCOSTANZO, V. (2006). ATM and ATR promote Mre11 dependent restart of collapsed replication forks and prevent accumulation of DNA breaks. EMBO J 25: 1764-1774.
84. TSUJI, T., LAU, E., CHIANG, G.G. and JIANG, W. (2008). The role of Dbf4/Drf1-dependent kinase Cdc7 in DNA-damage checkpoint control. Mol Cell 32: 862-869.
85. VAN, C., YAN, S., MICHAEL, W.M., WAGA, S. and CIMPRICH, K.A. (2010). Continued primer synthesis at stalled replication forks contributes to checkpoint activation. J Cell Biol 189: 233-246.
86. WANG, F., SHI, Z., CUI, Y., GUO, X., SHI, Y.B. and CHEN, Y. (2015). Targeted gene disruption in Xenopus laevis using CRISPR/Cas9. Cell Biosci 5: 15.
87. WANG, H., PENG, C., CHEN, Z., WANG, S., WANG, H.W., QIU, W., ZHAO, L., XU, R., LUO, H., CHEN, Y., CHEN, D., YOU, Y. and LIU, N. (2016). The error-prone DNA polymerase kappa promotes temozolomide resistance in glioblastoma through Rad17-dependent activation of ATR-Chk1 signaling. Cancer Res. 76. DOI: 10.1158/0008-5472.CAN-15-1884
88. WANG, L.C., STONE, S., HOATLIN, M.E. and GAUTIER, J. (2008). Fanconi anemia proteins stabilize replication forks. DNA Repair. 7: 1973-1981.
89. WEBER, A.M. and RYAN, A.J. (2015). ATM and ATR as therapeutic targets in cancer. Pharmacol Ther 149: 124-138.
90. WILLIAMS, H.L., GOTTESMAN, M.E. and GAUTIER, J. (2012). Replication-indepen-dent repair of DNA interstrand crosslinks. Mol Cell 47: 140-147.
91. WILLIS, J., DESTEPHANIS, D., PATEL, Y., GOWDA, V. and YAN, S. (2012). Study of the DNA damage checkpoint using Xenopus egg extracts. J Vis Exp. e4449.
92. WILLIS, J., PATEL, Y., LENTZ, B.L. and YAN, S. (2013). APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress. Proc Natl Acad Sci USA. 110: 10592-10597.
93. YAMANAKA, K., DORJSUREN, D., EOFF, R.L., EGLI, M., MALONEY, D.J., JADHAV, A., SIMEONOV, A. and LLOYD, R.S. (2012). Acomprehensive strategy to discover inhibitors of the translesion synthesis DNApolymerase kappa. PLoS One. 7: e45032.
94. YAN, S., LINDSAY, H.D. and MICHAEL, W.M. (2006). Direct requirement for Xmus101 in ATR-mediated phosphorylation of Claspin bound Chk1 during checkpoint signaling. J Cell Biol 173: 181-186.
95. YAN, S. and MICHAEL, W.M. (2009a). TopBP1 and DNA polymerase alpha-mediated recruitment of the 9-1-1 complex to stalled replication forks: implications for a replication restart-based mechanism for ATR checkpoint activation. Cell Cycle 8: 2877-2884.
96. YAN, S. and MICHAEL, W.M. (2009b). TopBP1 and DNA polymerase-alpha directly recruit the 9-1-1 complex to stalled DNA replication forks. J Cell Biol 184: 793-804.
97. YAN, S., SORRELL, M. and BERMAN, Z. (2014). Functional interplay between ATM/ ATR-mediated DNA damage response and DNA repair pathways in oxidative stress. Cell Mol Life Sci 71: 3951-3967.
98. YAN, S. and WILLIS, J. (2013). WD40-repeat protein WDR18 collaborates with TopBP1 to facilitate DNA damage checkpoint signaling. Biochem Biophys Res Commun 431: 466-471.
99. YOO, H.Y., KUMAGAI, A., SHEVCHENKO, A. and DUNPHY, W.G. (2004). Adaptation of a DNA replication checkpoint response depends upon inactivation of Claspin by the Polo-like kinase. Cell 117: 575-588.
100. YOU, Z., BAILIS, J.M., JOHNSON, S.A., DILWORTH, S.M. and HUNTER, T. (2007). Rapid activation of ATM on DNA flanking double-strand breaks. Nat Cell Biol 9: 1311-1318.
101. YOU, Z., CHAHWAN, C., BAILIS, J., HUNTER, T. and RUSSELL, P. (2005). ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1. Mol Cell Biol 25: 5363-5379.
102. ZEMAN, M.K. and CIMPRICH, K.A. (2013). Causes and consequences of replication stress. Nat Cell Biol 16: 2-9.
103. ZOU, L. and ELLEDGE, S.J. (2003). Sensing DNAdamage through ATRIP recognition of RPA-ssDNA complexes. Science 300: 1542-1548.