The Intra-S-Phase Checkpoint Affects both DNA Replication Initiation and Elongation: Single-Cell and -DNA Fiber Analyses

REFERENCES

• Anglana, M., F. Apiou, A. Bensimon, and M. Debatisse. 2003. Dynamics of DNA replication in mammalian somatic cells: nucleotide pool modulates origin choice and interorigin spacing. Cell 114:385–394.
   PubMed Web of Science ®Google Scholar
• Avemann, K., R. Knippers, T. Koller, and J. M. Sogo. 1988. Camptothecin, a specific inhibitor of type I DNA topoisomerase, induces DNA breakage at replication forks. Mol. Cell. Biol. 8:3026–3034.
   PubMed Web of Science ®Google Scholar
• Berezney, R., D. D. Dubey, and J. A. Huberman. 2000. Heterogeneity of eukaryotic replicons, replicon clusters, and replication foci. Chromosoma 108:471–484.
   PubMed Web of Science ®Google Scholar
• Bjornsti, M. A., P. Benedetti, G. A. Viglianti, and J. C. Wang. 1989. Expression of human DNA topoisomerase I in yeast cells lacking yeast DNA topoisomerase I: restoration of sensitivity of the cells to the antitumor drug camptothecin. Cancer Res. 49:6318–6323.
   PubMed Web of Science ®Google Scholar
• Bosco, E. E., C. N. Mayhew, R. F. Hennigan, J. Sage, T. Jacks, and E. S. Knudsen. 2004. RB signaling prevents replication-dependent DNA double-strand breaks following genotoxic insult. Nucleic Acids Res. 32:25–34.
   PubMedGoogle Scholar
• Busby, E. C., D. F. Leistritz, R. T. Abraham, L. M. Karnitz, and J. N. Sarkaria. 2000. The radiosensitizing agent 7-hydroxystaurosporine (UCN-01) inhibits the DNA damage checkpoint kinase hChk1. Cancer Res. 60:2108–2112.
   PubMed Web of Science ®Google Scholar
• Champoux, J. J. 2001. DNA topoisomerase I-mediated nicking of circular duplex DNA. Methods Mol. Biol. 95:81–87.
   PubMedGoogle Scholar
• Champoux, J. J. 2001. DNA topoisomerases: structure, function, and mechanism. Annu. Rev. Biochem. 70:369–413.
   PubMed Web of Science ®Google Scholar
• Chastain, P. D., II, T. P. Heffernan, K. R. Nevis, L. Lin, W. K. Kaufmann, D. G. Kaufman, and M. Cordeiro-Stone. 2006. Checkpoint regulation of replication dynamics in UV-irradiated human cells. Cell Cycle 5:2160–2167.
   PubMed Web of Science ®Google Scholar
• Cliby, W. A., K. A. Lewis, K. K. Lilly, and S. H. Kaufmann. 2002. S phase and G2 arrests induced by topoisomerase I poisons are dependent on ATR kinase function. J. Biol. Chem. 277:1599–1606.
   PubMedGoogle Scholar
• Conti, C., S. Caburet, and A. Bensimon. 2001. Targeting the molecular mechanism of DNA replication. Drug Discov. Today 6:786–792.
   PubMedGoogle Scholar
• Covey, J. M., C. Jaxel, K. W. Kohn, and Y. Pommier. 1989. Protein-linked DNA strand breaks induced in mammalian cells by camptothecin, an inhibitor of topoisomerase I. Cancer Res. 49:5016–5022.
   PubMedGoogle Scholar
• Dimitrova, D. S., and R. Berezney. 2002. The spatio-temporal organization of DNA replication sites is identical in primary, immortalized, and transformed mammalian cells. J. Cell Sci. 115:4037–4051.
   PubMed Web of Science ®Google Scholar
• Dimitrova, D. S., and D. M. Gilbert. 1999. The spatial position and replication timing of chromosomal domains are both established in early G1 phase. Mol. Cell 4:983–993.
   PubMed Web of Science ®Google Scholar
• Feijoo, C., C. Hall-Jackson, R. Wu, D. Jenkins, J. Leitch, D. M. Gilbert, and C. Smythe. 2001. Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing. J. Cell Biol. 154:913–923.
   PubMed Web of Science ®Google Scholar
• Furuta, T., R. L. Hayward, L. H. Meng, H. Takemura, G. J. Aune, W. M. Bonner, M. I. Aladjem, K. W. Kohn, and Y. Pommier. 2006. p21(CDKN1A) allows the repair of replication-mediated DNA double-strand breaks induced by topoisomerase I and is inactivated by the checkpoint kinase inhibitor 7-hydroxystaurosporine. Oncogene 25:2839–2849.
   PubMed Web of Science ®Google Scholar
• Furuta, T., H. Takemura, Z. Y. Liao, G. J. Aune, C. Redon, O. A. Sedelnikova, D. R. Pilch, E. P. Rogakou, A. Celeste, H. T. Chen, A. Nussenzweig, M. I. Aladjem, W. M. Bonner, and Y. Pommier. 2003. Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes. J. Biol. Chem. 278:20303–20312.
   PubMed Web of Science ®Google Scholar
• Goldwasser, F., T. Shimizu, J. Jackman, Y. Hoki, P. M. O'Connor, K. W. Kohn, and Y. Pommier. 1996. Correlations between S and G2 arrest and the cytotoxicity of camptothecin in human colon carcinoma cells. Cancer Res. 56:4430–4437.
   PubMed Web of Science ®Google Scholar
• Graves, P. R., L. Yu, J. K. Schwarz, J. Gales, E. A. Sausville, P. M. O'Connor, and H. Piwnica-Worms. 2000. The Chk1 protein kinase and the Cdc25C regulatory pathways are targets of the anticancer agent UCN-01. J. Biol. Chem. 275:5600–5605.
   PubMed Web of Science ®Google Scholar
• Holm, C., J. M. Covey, D. Kerrigan, and Y. Pommier. 1989. Differential requirement of DNA replication for the cytotoxicity of DNA topoisomerase I and II inhibitors in Chinese hamster DC3F cells. Cancer Res. 49:6365–6368.
   PubMed Web of Science ®Google Scholar
• Hsiang, Y. H., R. Hertzberg, S. Hecht, and L. F. Liu. 1985. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J. Biol. Chem. 260:14873–14878.
   PubMed Web of Science ®Google Scholar
• Hsiang, Y. H., M. G. Lihou, and L. F. Liu. 1989. Arrest of replication forks by drug-stabilized topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin. Cancer Res. 49:5077–5082.
   PubMed Web of Science ®Google Scholar
• Jackson, D. A., and A. Pombo. 1998. Replicon clusters are stable units of chromosome structure: evidence that nuclear organization contributes to the efficient activation and propagation of S phase in human cells. J. Cell Biol. 140:1285–1295.
   PubMed Web of Science ®Google Scholar
• Kastan, M. B., and J. Bartek. 2004. Cell-cycle checkpoints and cancer. Nature 432:316–323.
   PubMed Web of Science ®Google Scholar
• Kaufmann, W. K., J. C. Boyer, L. L. Estabrooks, and S. J. Wilson. 1991. Inhibition of replicon initiation in human cells following stabilization of topoisomerase-DNA cleavable complexes. Mol. Cell. Biol. 11:3711–3718.
   PubMed Web of Science ®Google Scholar
• Kohn, E. A., N. D. Ruth, M. K. Brown, M. Livingstone, and A. Eastman. 2002. Abrogation of the S phase DNA damage checkpoint results in S phase progression or premature mitosis depending on the concentration of 7-hydroxystaurosporine and the kinetics of Cdc25C activation. J. Biol. Chem. 277:26553–26564.
   PubMedGoogle Scholar
• Larner, J. M., H. Lee, R. D. Little, P. A. Dijkwel, C. L. Schildkraut, and J. L. Hamlin. 1999. Radiation down-regulates replication origin activity throughout the S phase in mammalian cells. Nucleic Acids Res. 27:803–809.
   PubMedGoogle Scholar
• Lee, S. I., M. K. Brown, and A. Eastman. 1999. Comparison of the efficacy of 7-hydroxystaurosporine (UCN-01) and other staurosporine analogs to abrogate cisplatin-induced cell cycle arrest in human breast cancer cell lines. Biochem. Pharmacol. 58:1713–1721.
   PubMedGoogle Scholar
• Ma, H., J. Samarabandu, R. S. Devdhar, R. Acharya, P. C. Cheng, C. Meng, and R. Berezney. 1998. Spatial and temporal dynamics of DNA replication sites in mammalian cells. J. Cell Biol. 143:1415–1425.
   PubMed Web of Science ®Google Scholar
• Marheineke, K., and O. Hyrien. 2004. Control of replication origin density and firing time in Xenopus egg extracts: role of a caffeine-sensitive, ATR-dependent checkpoint. J. Biol. Chem. 279:28071–28081.
   PubMed Web of Science ®Google Scholar
• Merrick, C. J., D. Jackson, and J. F. Diffley. 2004. Visualization of altered replication dynamics after DNA damage in human cells. J. Biol. Chem. 279:20067–20075.
   PubMed Web of Science ®Google Scholar
• Miao, H., J. A. Seiler, and W. C. Burhans. 2003. Regulation of cellular and SV40 virus origins of replication by Chk1-dependent intrinsic and UVC radiation-induced checkpoints. J. Biol. Chem. 278:4295–4304.
   PubMedGoogle Scholar
• Monks, A., E. D. Harris, A. Vaigro-Wolff, C. D. Hose, J. W. Connelly, and E. A. Sausville. 2000. UCN-01 enhances the in vitro toxicity of clinical agents in human tumor cell lines. Investig. New Drugs 18:95–107.
   PubMed Web of Science ®Google Scholar
• Nakamura, H., T. Morita, and C. Sato. 1986. Structural organizations of replicon domains during DNA synthetic phase in the mammalian nucleus. Exp. Cell Res. 165:291–297.
   PubMed Web of Science ®Google Scholar
• Ni, Z. J., P. Barsanti, N. Brammeier, A. Diebes, D. J. Poon, S. Ng, S. Pecchi, K. Pfister, P. A. Renhowe, S. Ramurthy, A. S. Wagman, D. E. Bussiere, V. Le, Y. Zhou, J. M. Jansen, S. Ma, and T. G. Gesner. 2006. 4-(Aminoalkylamino)-3-benzimidazole-quinolinones as potent CHK-1 inhibitors. Bioorg. Med. Chem. Lett. 16:3121–3124.
   PubMed Web of Science ®Google Scholar
• Nitiss, J., and J. C. Wang. 1988. DNA topoisomerase-targeting antitumor drugs can be studied in yeast. Proc. Natl. Acad. Sci. USA 85:7501–7505.
   PubMed Web of Science ®Google Scholar
• O'Keefe, R. T., S. C. Henderson, and D. L. Spector. 1992. Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific alpha-satellite DNA sequences. J. Cell Biol. 116:1095–1110.
   PubMed Web of Science ®Google Scholar
• Painter, R. B. 1981. Radioresistant DNA synthesis: an intrinsic feature of ataxia telangiectasia. Mutat. Res. 84:183–190.
   PubMedGoogle Scholar
• Pommier, Y. 2006. Topoisomerase I inhibitors, camptothecins, and beyond. Nat. Rev. Cancer 6:789–802.
   PubMed Web of Science ®Google Scholar
• Pommier, Y., J. M. Barcelo, V. A. Rao, O. Sordet, A. G. Jobson, L. Thibaut, Z.-H. Miao, J. A. Seiler, H. Zhang, C. Marchand, K. Agama, J. L. Nitiss, and C. Redon. 2006. Repair of topisomerase 1-mediated DNA damage. Prog. Nucleic Acid Res. 81:179–229.
   PubMed Web of Science ®Google Scholar
• Pommier, Y., and R. B. Diasio. 2006. Pharmacological agents that target DNA replication in DNA replication and human disease. Cold Spring Harbor Laboratory Press, New York, NY.
   Google Scholar
• Pommier, Y., C. Redon, V. A. Rao, J. A. Seiler, O. Sordet, H. Takemura, S. Antony, L. Meng, Z. Liao, G. Kohlhagen, H. Zhang, and K. W. Kohn. 2003. Repair of and checkpoint response to topoisomerase I-mediated DNA damage. Mutat. Res. 532:173–203.
   PubMed Web of Science ®Google Scholar
• Rogakou, E. P., C. Boon, C. Redon, and W. M. Bonner. 1999. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J. Cell Biol. 146:905–916.
   PubMed Web of Science ®Google Scholar
• Rogakou, E. P., D. R. Pilch, A. H. Orr, V. S. Ivanova, and W. M. Bonner. 1998. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem. 273:5858–5868.
   PubMed Web of Science ®Google Scholar
• Ryan, A. J., S. Squires, H. L. Strutt, and R. T. Johnson. 1991. Camptothecin cytotoxicity in mammalian cells is associated with the induction of persistent double strand breaks in replicating DNA. Nucleic Acids Res. 19:3295–3300.
   PubMed Web of Science ®Google Scholar
• Santocanale, C., and J. F. Diffley. 1998. A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication. Nature 395:615–618.
   PubMed Web of Science ®Google Scholar
• Sedelnikova, O. A., E. P. Rogakou, I. G. Panyutin, and W. M. Bonner. 2002. Quantitative detection of 125IdU-induced DNA double-strand breaks with γ-H2AX antibody. Radiat. Res. 158:486–492.
   PubMed Web of Science ®Google Scholar
• Shao, R. G., C. X. Cao, T. Shimizu, P. M. O'Connor, K. W. Kohn, and Y. Pommier. 1997. Abrogation of an S-phase checkpoint and potentiation of camptothecin cytotoxicity by 7-hydroxystaurosporine (UCN-01) in human cancer cell lines, possibly influenced by p53 function. Cancer Res. 57:4029–4035.
   PubMedGoogle Scholar
• Shao, R. G., C. X. Cao, H. Zhang, K. W. Kohn, M. S. Wold, and Y. Pommier. 1999. Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes. EMBO J. 18:1397–1406.
   PubMedGoogle Scholar
• Shechter, D., V. Costanzo, and J. Gautier. 2004. ATR and ATM regulate the timing of DNA replication origin firing. Nat. Cell Biol. 6:648–655.
   PubMed Web of Science ®Google Scholar
• Shechter, D., and J. Gautier. 2005. ATM and ATR check in on origins: a dynamic model for origin selection and activation. Cell Cycle 4:235–238.
   PubMedGoogle Scholar
• Shi, Z., A. Azuma, D. Sampath, Y. X. Li, P. Huang, and W. Plunkett. 2001. S-phase arrest by nucleoside analogues and abrogation of survival without cell cycle progression by 7-hydroxystaurosporine. Cancer Res. 61:1065–1072.
   PubMed Web of Science ®Google Scholar
• Shiloh, Y. 2003. ATM: ready, set, go. Cell Cycle 2:116–117.
   PubMed Web of Science ®Google Scholar
• Shirahige, K., Y. Hori, K. Shiraishi, M. Yamashita, K. Takahashi, C. Obuse, T. Tsurimoto, and H. Yoshikawa. 1998. Regulation of DNA-replication origins during cell-cycle progression. Nature 395:618–621.
   PubMed Web of Science ®Google Scholar
• Snapka, R. M. 1986. Topoisomerase inhibitors can selectively interfere with different stages of simian virus 40 DNA replication. Mol. Cell. Biol. 6:4221–4227.
   PubMed Web of Science ®Google Scholar
• Soe, K., A. Rockstroh, P. Schache, and F. Grosse. 2004. The human topoisomerase I damage response plays a role in apoptosis. DNA Repair 3:387–393.
   PubMedGoogle Scholar
• Sordet, O., Q. A. Khan, and Y. Pommier. 2004. Apoptotic topoisomerase I-DNA complexes induced by oxygen radicals and mitochondrial dysfunction. Cell Cycle 3:1095–1097.
   PubMedGoogle Scholar
• Strumberg, D., A. A. Pilon, M. Smith, R. Hickey, L. Malkas, and Y. Pommier. 2000. Conversion of topoisomerase I cleavage complexes on the leading strand of ribosomal DNA into 5′-phosphorylated DNA double-strand breaks by replication runoff. Mol. Cell. Biol. 20:3977–3987.
   PubMed Web of Science ®Google Scholar
• Takemura, H., V. A. Rao, O. Sordet, T. Furuta, Z. H. Miao, L. Meng, H. Zhang, and Y. Pommier. 2006. Defective Mre11-dependent activation of Chk2 by ataxia telangiectasia mutated in colorectal carcinoma cells in response to replication-dependent DNA double strand breaks. J. Biol. Chem. 281:30814–30823.
   PubMed Web of Science ®Google Scholar
• Tsao, Y. P., A. Russo, G. Nyamuswa, R. Silber, and L. F. Liu. 1993. Interaction between replication forks and topoisomerase I-DNA cleavable complexes: studies in a cell-free SV40 DNA replication system. Cancer Res. 53:5908–5914.
   PubMed Web of Science ®Google Scholar
• Tse, A. N., K. G. Rendahl, T. Sheikh, H. Cheema, K. Aardalen, M. Embry, S. Ma, E. J. Moler, Z. J. Ni, D. E. Lopes de Menezes, B. Hibner, T. G. Gesner, and G. K. Schwartz. 2007. CHIR-124, a novel potent inhibitor of Chk1, potentiates the cytotoxicity of topoisomerase I poisons in vitro and in vivo. Clin. Cancer Res. 13:591–602.
   PubMed Web of Science ®Google Scholar
• Tse, A. N., and G. K. Schwartz. 2004. Potentiation of cytotoxicity of topoisomerase I poison by concurrent and sequential treatment with the checkpoint inhibitor UCN-01 involves disparate mechanisms resulting in either p53-independent clonogenic suppression or p53-dependent mitotic catastrophe. Cancer Res. 64:6635–6644.
   PubMedGoogle Scholar
• Wang, J. C. 2002. Cellular roles of DNA topoisomerases: a molecular perspective. Nat. Rev. Mol. Cell. Biol. 3:430–440.
   PubMed Web of Science ®Google Scholar
• Wang, J. L., X. Wang, H. Wang, G. Iliakis, and Y. Wang. 2002. CHK1-regulated S-phase checkpoint response reduces camptothecin cytotoxicity. Cell Cycle 1:267–272.
   PubMedGoogle Scholar
• Wang, Q., S. Fan, A. Eastman, P. J. Worland, E. A. Sausville, and P. M. O'Connor. 1996. UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53. J. Natl. Cancer Inst. 88:956–965.
   PubMed Web of Science ®Google Scholar
• Wang, X., J. Guan, B. Hu, R. S. Weiss, G. Iliakis, and Y. Wang. 2004. Involvement of Hus1 in the chain elongation step of DNA replication after exposure to camptothecin or ionizing radiation. Nucleic Acids Res. 32:767–775.
   PubMed Web of Science ®Google Scholar
• Wang, Y., A. R. Perrault, and G. Iliakis. 1997. Down-regulation of DNA replication in extracts of camptothecin-treated cells: activation of an S-phase checkpoint? Cancer Res. 57:1654–1659.
   PubMedGoogle Scholar
• Xiao, Z., Z. Chen, A. H. Gunasekera, T. J. Sowin, S. H. Rosenberg, S. Fesik, and H. Zhang. 2003. Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents. J. Biol. Chem. 278:21767–21773.
   PubMed Web of Science ®Google Scholar
• You, Z., L. Kong, and J. Newport. 2002. The role of single-stranded DNA and polymerase alpha in establishing the ATR, Hus1 DNA replication checkpoint. J. Biol. Chem. 277:27088–27093.
   PubMed Web of Science ®Google Scholar
• Zachos, G., M. D. Rainey, and D. A. Gillespie. 2003. Chk1-deficient tumour cells are viable but exhibit multiple checkpoint and survival defects. EMBO J. 22:713–723.
   PubMed Web of Science ®Google Scholar