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Science 4 December 1998:
Vol. 282. no. 5395, pp. 1893 - 1897
DOI: 10.1126/science.282.5395.1893
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Reports

Linkage of ATM to Cell Cycle Regulation by the Chk2 Protein Kinase

Shuhei Matsuoka, Mingxia Huang, Stephen J. Elledge *

In response to DNA damage and replication blocks, cells prevent cell cycle progression through the control of critical cell cycle regulators. We identified Chk2, the mammalian homolog of the Saccharomyces cerevisiae Rad53 and Schizosaccharomyces pombe Cds1 protein kinases required for the DNA damage and replication checkpoints. Chk2 was rapidly phosphorylated and activated in response to replication blocks and DNA damage; the response to DNA damage occurred in an ataxia telangiectasia mutated (ATM)-dependent manner. In vitro, Chk2 phosphorylated Cdc25C on serine-216, a site known to be involved in negative regulation of Cdc25C. This is the same site phosphorylated by the protein kinase Chk1, which suggests that, in response to DNA damage and DNA replicational stress, Chk1 and Chk2 may phosphorylate Cdc25C to prevent entry into mitosis.

Howard Hughes Medical Institute, Verna and Marrs McLean Department of Biochemistry and Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
*   To whom correspondence should be addressed. E-mail: selledge{at}bcm.tmc.edu

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Circulation 110, 3136-3142
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Locked Nucleic Acid-Enhanced Detection of 1100delC*CHEK2 Germ-Line Mutation in Spanish Patients with Hematologic Malignancies.
M. Collado, O. Landt, E. Barragan, U. Lass, J. Cervera, M. A. Sanz, and P. Bolufer (2004)
Clin. Chem. 50, 2201-2204
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Germline CHEK2*1100delC mutations in breast cancer patients with multiple primary cancers.
J Huang, S M Domchek, M S Brose, T R Rebbeck, K L Nathanson, and B L Weber (2004)
J. Med. Genet. 41, e120
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ATM-dependent CHK2 Activation Induced by Anticancer Agent, Irofulven.
J. Wang, T. Wiltshire, Y. Wang, C. Mikell, J. Burks, C. Cunningham, E. S. Van Laar, S. J. Waters, E. Reed, and W. Wang (2004)
J. Biol. Chem. 279, 39584-39592
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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.
A. N. Tse and G. K. Schwartz (2004)
Cancer Res. 64, 6635-6644
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Deletion of Mouse Rad9 Causes Abnormal Cellular Responses to DNA Damage, Genomic Instability, and Embryonic Lethality.
K. M. Hopkins, W. Auerbach, X. Y. Wang, M. P. Hande, H. Hang, D. J. Wolgemuth, A. L. Joyner, and H. B. Lieberman (2004)
Mol. Cell. Biol. 24, 7235-7248
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BRCA1-BARD1 Complexes Are Required for p53Ser-15 Phosphorylation and a G1/S Arrest following Ionizing Radiation-induced DNA Damage.
M. Fabbro, K. Savage, K. Hobson, A. J. Deans, S. N. Powell, G. A. McArthur, and K. K. Khanna (2004)
J. Biol. Chem. 279, 31251-31258
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Differentiation-Induced Radioresistance in Muscle Cells.
L. Latella, J. Lukas, C. Simone, P. L. Puri, and J. Bartek (2004)
Mol. Cell. Biol. 24, 6350-6361
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Binding of 14-3-3{beta} but not 14-3-3{sigma} controls the cytoplasmic localization of CDC25B: binding site preferences of 14-3-3 subtypes and the subcellular localization of CDC25B.
S. Uchida, A. Kuma, M. Ohtsubo, M. Shimura, M. Hirata, H. Nakagama, T. Matsunaga, Y. Ishizaka, and K. Yamashita (2004)
J. Cell Sci. 117, 3011-3020
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Negative Regulation of Chk2 Expression by p53 Is Dependent on the CCAAT-binding Transcription Factor NF-Y.
T. Matsui, Y. Katsuno, T. Inoue, F. Fujita, T. Joh, H. Niida, H. Murakami, M. Itoh, and M. Nakanishi (2004)
J. Biol. Chem. 279, 25093-25100
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Sulforaphane-induced G2/M Phase Cell Cycle Arrest Involves Checkpoint Kinase 2-mediated Phosphorylation of Cell Division Cycle 25C.
S. V. Singh, A. Herman-Antosiewicz, A. V. Singh, K. L. Lew, S. K. Srivastava, R. Kamath, K. D. Brown, L. Zhang, and R. Baskaran (2004)
J. Biol. Chem. 279, 25813-25822
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The Molecular Pathology of Primary Immunodeficiencies.
M. S. Lim and K. S.J. Elenitoba-Johnson (2004)
J. Mol. Diagn. 6, 59-83
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DNA damage responses triggered by a highly cytotoxic monofunctional DNA alkylator, hedamycin, a pluramycin antitumor antibiotic.
L. C. Tu, T. Melendy, and T. A. Beerman (2004)
Mol. Cancer Ther. 3, 577-586
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Rad9 Protects Cells from Topoisomerase Poison-induced Cell Death.
D. Loegering, S. J. H. Arlander, J. Hackbarth, B. T. Vroman, P. Roos-Mattjus, K. M. Hopkins, H. B. Lieberman, L. M. Karnitz, and S. H. Kaufmann (2004)
J. Biol. Chem. 279, 18641-18647
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Human Claspin works with BRCA1 to both positively and negatively regulate cell proliferation.
S.-Y. Lin, K. Li, G. S. Stewart, and S. J. Elledge (2004)
PNAS 101, 6484-6489
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A Cleaved Form of MAGE-A4 Binds to Miz-1 and Induces Apoptosis in Human Cells.
T. Sakurai, K. Itoh, H. Higashitsuji, T. Nagao, K. Nonoguchi, T. Chiba, and J. Fujita (2004)
J. Biol. Chem. 279, 15505-15514
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Apoptosis Associated with Deregulated E2F Activity Is Dependent on E2F1 and Atm/Nbs1/Chk2.
H. A. Rogoff, M. T. Pickering, F. M. Frame, M. E. Debatis, Y. Sanchez, S. Jones, and T. F. Kowalik (2004)
Mol. Cell. Biol. 24, 2968-2977
   Abstract »    Full Text »    PDF »


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