WRN Is Required for ATM Activation and the S-Phase Checkpoint in Response to Interstrand Cross-Link–Induced DNA Double-Strand Breaks

Molecular Biology of the Cell - Tập 19 Số 9 - Trang 3923-3933 - 2008
Wen‐Hsing Cheng1,2, Diana Muftic3, Meltem Müftüoğlu4, Lale Dawut4, Christa Morris5, Thomas Helleday3, Yosef Shiloh6, Vilhelm A. Bohr4
1Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742
2Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 USA
3Department of Genetics, Microbiology, and Toxicology, Arrhenius Laboratory, Stockholm University, S-106 91 Stockholm, Sweden; and
4*Laboratory of Molecular Gerontology and
5Flow Cytometry Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224;
6David and Inez Myers Laboratory for Genetic Research, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel

Tóm tắt

Werner syndrome (WS) is a human genetic disorder characterized by extensive clinical features of premature aging. Ataxia-telengiectasia (A-T) is a multisystem human genomic instability syndrome that includes premature aging in some of the patients. WRN and ATM, the proteins defective in WS and A-T, respectively, play significant roles in the maintenance of genomic stability and are involved in several DNA metabolic pathways. A role for WRN in DNA repair has been proposed; however, this study provides evidence that WRN is also involved in ATM pathway activation and in a S-phase checkpoint in cells exposed to DNA interstrand cross-link–induced double-strand breaks. Depletion of WRN in such cells by RNA interference results in an intra-S checkpoint defect, and interferes with activation of ATM as well as downstream phosphorylation of ATM target proteins. Treatment of cells under replication stress with the ATM kinase inhibitor KU 55933 results in a S-phase checkpoint defect similar to that observed in WRN shRNA cells. Moreover, γH2AX levels are higher in WRN shRNA cells than in control cells 6 and 16 h after exposure to psoralen DNA cross-links. These results suggest that WRN and ATM participate in a replication checkpoint response, in which WRN facilitates ATM activation in cells with psoralen DNA cross-link–induced collapsed replication forks.

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Tài liệu tham khảo

Abraham R. T., 2004, DNA Repair, 3, 883, 10.1016/j.dnarep.2004.04.002

Abraham R. T., 2001, Genes Dev, 15, 2177, 10.1101/gad.914401

Ajiro K., 1996, J. Biol. Chem, 271, 13197, 10.1074/jbc.271.22.13197

Alderton G. K., 2006, Nat. Cell Biol, 8, 725, 10.1038/ncb1431

Bakkenist C. J., 2003, Nature, 421, 499, 10.1038/nature01368

Balajee A. S., 2001, Nucleic Acids Res, 29, 1341, 10.1093/nar/29.6.1341

Bartek J., 2004, Nat. Rev. Mol. Cell Biol, 5, 792, 10.1038/nrm1493

Bartkova J., 2006, Nature, 444, 633, 10.1038/nature05268

Biton S., 2006, J. Biol. Chem, 281, 17482, 10.1074/jbc.M601895200

Bohr V. A., 2001, Environ. Mol. Mutagen, 38, 227, 10.1002/em.1076

Bolderson E., 2004, Hum. Mol. Genet, 13, 2937, 10.1093/hmg/ddh316

Brosh R. M., 1999, J. Biol. Chem, 274, 18341, 10.1074/jbc.274.26.18341

Bryant H. E., 2006, Nucleic Acids Res, 34, 1685, 10.1093/nar/gkl108

Bryant H. E., 2005, Nature, 434, 913, 10.1038/nature03443

Cheng W. H., 2006, Nucleic Acids Res, 34, 2751, 10.1093/nar/gkl362

Cheng W. H., 2005, FEBS Lett, 579, 1350, 10.1016/j.febslet.2005.01.028

Cheng W. H., 2004, J. Biol. Chem, 279, 21169, 10.1074/jbc.M312770200

Cheng W. H., 2003, Mol. Cell. Biol, 23, 6385, 10.1128/MCB.23.18.6385-6395.2003

Chun H. H., 2004, DNA Repair, 3, 1187, 10.1016/j.dnarep.2004.04.010

Constantinou A., 2000, EMBO Rep, 1, 80, 10.1093/embo-reports/kvd004

Crabbe L., 2004, Science, 306, 1951, 10.1126/science.1103619

Cuadrado M., 2006, J. Exp. Med, 203, 297, 10.1084/jem.20051923

Davalos A. R., 2004, Cell Cycle, 3, 1579, 10.4161/cc.3.12.1286

Farmer H., 2005, Nature, 434, 917, 10.1038/nature03445

Frei C., 2000, Genes Dev, 14, 81, 10.1101/gad.14.1.81

Gatei M., 2000, Cancer Res, 60, 3299

Gatei M., 2003, J. Biol. Chem, 278, 14806, 10.1074/jbc.M210862200

Goldberg M., 2003, Nature, 421, 952, 10.1038/nature01445

Gray M. D., 1997, Nat. Genet, 17, 100, 10.1038/ng0997-100

Huang S., 1998, Nat. Genet, 20, 114, 10.1038/2410

Huyen Y., 2004, Nature, 432, 406, 10.1038/nature03114

Jaspers N. G., 2006, Methods Mol. Biol, 314, 51, 10.1385/1-59259-973-7:051

Jazayeri A., 2006, Nat. Cell Biol, 8, 37, 10.1038/ncb1337

Karmakar P., 2005, Mech. Ageing Dev, 126, 1146, 10.1016/j.mad.2005.06.004

Kim S. T., 2002, Genes Dev, 16, 560, 10.1101/gad.970602

Kitagawa R., 2004, Genes Dev, 18, 1423, 10.1101/gad.1200304

Kozlov S. V., 2006, EMBO J, 25, 3504, 10.1038/sj.emboj.7601231

Kruhlak M. J., 2006, J. Cell Biol, 172, 823, 10.1083/jcb.200510015

Lan L., 2005, J. Cell Sci, 118, 4153, 10.1242/jcs.02544

Laud P. R., 2005, Genes Dev, 19, 2560, 10.1101/gad.1321305

Lebel M., 1999, J. Biol. Chem, 274, 37795, 10.1074/jbc.274.53.37795

Lee J. H., 2005, Science, 308, 551, 10.1126/science.1108297

Liberi G., 2005, Genes Dev, 19, 339, 10.1101/gad.322605

Lou Z, 2006, Mol. Cell, 21, 187, 10.1016/j.molcel.2005.11.025

Lundin C., 2002, Mol. Cell. Biol, 22, 5869, 10.1128/MCB.22.16.5869-5878.2002

Majumdar A., 1998, Nat. Genet, 20, 212, 10.1038/2530

Opresko P. L., 2004, J. Biol. Chem, 279, 18099, 10.1074/jbc.R300034200

Opresko P. L., 2004, Mol. Cell, 14, 763, 10.1016/j.molcel.2004.05.023

Pichierri P., 2004, EMBO J, 23, 1178, 10.1038/sj.emboj.7600113

Pichierri P., 2003, Oncogene, 22, 1491, 10.1038/sj.onc.1206169

Pommier Y., 2003, Mutat. Res, 532, 173, 10.1016/j.mrfmmm.2003.08.016

Poot M., 2002, FASEB J, 16, 757, 10.1096/fj.01-0906fje

Poot M., 1992, Exp. Cell Res, 202, 267, 10.1016/0014-4827(92)90074-I

Poot M., 2001, FASEB J, 15, 1224, 10.1096/fj.00-0611fje

Prince P. R., 2001, Genes Dev, 15, 933, 10.1101/gad.877001

Rothfuss A., 2004, Mol. Cell. Biol, 24, 123, 10.1128/MCB.24.1.123-134.2004

Saintigny Y., 2002, Mol. Cell. Biol, 22, 6971, 10.1128/MCB.22.20.6971-6978.2002

Saleh-Gohari N., 2005, Mol. Cell. Biol, 25, 7158, 10.1128/MCB.25.16.7158-7169.2005

Schultz L. B., 2000, J. Cell Biol, 151, 1381, 10.1083/jcb.151.7.1381

Shechter D., 2004, Nat. Cell Biol, 6, 648, 10.1038/ncb1145

Shechter D., 2004, DNA Repair, 3, 901, 10.1016/j.dnarep.2004.03.020

Shiloh Y., 2003, Nat. Rev. Cancer, 3, 155, 10.1038/nrc1011

Shiloh Y., 2006, Trends Biochem. Sci, 31, 402, 10.1016/j.tibs.2006.05.004

Stewart E., 1997, EMBO J, 16, 2682, 10.1093/emboj/16.10.2682

Stiff T., 2006, EMBO J, 25, 5775, 10.1038/sj.emboj.7601446

Stracker T. H., 2004, DNA Repair, 3, 845, 10.1016/j.dnarep.2004.03.014

Takeuchi F., 1982, Hum. Genet, 60, 365, 10.1007/BF00569220

Turaga R., 2007, Aging Cell, 6, 471, 10.1111/j.1474-9726.2007.00301.x

Tauchi H., 2002, Nature, 420, 93, 10.1038/nature01125

Trenz K., 2006, EMBO J, 25, 1764, 10.1038/sj.emboj.7601045

Uziel T., 2003, EMBO J, 22, 5612, 10.1093/emboj/cdg541

von Kobbe C., 2003, J. Biol. Chem, 278, 52997, 10.1074/jbc.M308338200

Xu B., 2001, Mol. Cell. Biol, 21, 3445, 10.1128/MCB.21.10.3445-3450.2001

Yan H., 1998, Nat. Genet, 19, 375, 10.1038/1263

Yannone S. M., 2001, J. Biol. Chem, 276, 38242, 10.1074/jbc.M101913200

Yu C. E., 1996, Science, 272, 258, 10.1126/science.272.5259.258

Ziv Y., 2006, Nat. Cell Biol, 8, 870, 10.1038/ncb1446

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Molecular Biology of the Cell

Tập 19 Số 9

3923-3933

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