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Science 19 January 1996:
Vol. 271. no. 5247, pp. 353 - 356
DOI: 10.1126/science.271.5247.353
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Reports

rad-Dependent Response of the chk1-Encoded Protein Kinase at the DNA Damage Checkpoint

Nancy C. Walworth (1) and Rene Bernards

Exposure of eukaryotic cells to agents that generate DNA damage results in transient arrest of progression through the cell cycle. In fission yeast, the DNA damage checkpoint associated with cell cycle arrest before mitosis requires the protein kinase p56chk1. DNA damage induced by ultraviolet light, gamma radiation, or a DNA-alkylating agent has now been shown to result in phosphorylation of p56chk1. This phosphorylation decreased the mobility of p56chk1 on SDS-polyacrylamide gel electrophoresis and was abolished by a mutation in the p56chk1 catalytic domain, suggesting that it might represent autophosphorylation. Phosphorylation of p56chk1 did not occur when other checkpoint genes were inactive. Thus, p56chk1 appears to function downstream of several of the known Schizosaccharomyces pombe checkpoint gene products, including that encoded by rad3, a gene with sequence similarity to the ATM gene mutated in patients with ataxia telangiectasia. The phosphorylation of p56chk1 provides an assayable biochemical response to activation of the DNA damage checkpoint in the G2 phase of the cell cycle.


Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.
(1) To whom correspondence should be directed at present address: Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854-5635, USA.


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   Abstract »    Full Text »    PDF »
Replication Factor C3 of Schizosaccharomyces pombe, a Small Subunit of Replication Factor C Complex, Plays a Role in Both Replication and Damage Checkpoints.
M. Shimada, D. Okuzaki, S. Tanaka, T. Tougan, K. K. Tamai, C. Shimoda, and H. Nojima (1999)
Mol. Biol. Cell 10, 3991-4003
   Abstract »    Full Text »
Control of the DNA Damage Checkpoint by Chk1 and Rad53 Protein Kinases Through Distinct Mechanisms.
Y. Sanchez, J. Bachant, H. Wang, F. Hu, D. Liu, M. Tetzlaff, and S. J. Elledge (1999)
Science 286, 1166-1171
   Abstract »    Full Text »
DNA Damage and Replication Checkpoints in Fission Yeast Require Nuclear Exclusion of the Cdc25 Phosphatase via 14-3-3 Binding.
Y. Zeng and H. Piwnica-Worms (1999)
Mol. Cell. Biol. 19, 7410-7419
   Abstract »    Full Text »    PDF »
Role of Human Cds1 (Chk2) Kinase in DNA Damage Checkpoint and Its Regulation by p53.
K. Tominaga, H. Morisaki, Y. Kaneko, A. Fujimoto, T. Tanaka, M. Ohtsubo, M. Hirai, H. Okayama, K. Ikeda, and M. Nakanishi (1999)
J. Biol. Chem. 274, 31463-31467
   Abstract »    Full Text »    PDF »
Meiotic DNA replication checkpoint control in fission yeast.
H. Murakami and P. Nurse (1999)
Genes & Dev. 13, 2581-2593
   Abstract »    Full Text »
Requirement of Sequences outside the Conserved Kinase Domain of Fission Yeast Rad3p for Checkpoint Control.
C. R. Chapman, S. T. Evans, A. M. Carr, and T. Enoch (1999)
Mol. Biol. Cell 10, 3223-3238
   Abstract »    Full Text »
A quantitative analysis of the kinetics of the G2 DNA damage checkpoint system.
B. D. Aguda (1999)
PNAS 96, 11352-11357
   Abstract »    Full Text »    PDF »
Inhibition of ATM and ATR Kinase Activities by the Radiosensitizing Agent, Caffeine.
J. N. Sarkaria, E. C. Busby, R. S. Tibbetts, P. Roos, Y. Taya, L. M. Karnitz, and R. T. Abraham (1999)
Cancer Res. 59, 4375-4382
   Abstract »    Full Text »    PDF »
Rad18 Is Required for DNA Repair and Checkpoint Responses in Fission Yeast.
H. M. Verkade, S. J. Bugg, H. D. Lindsay, A. M. Carr, and M. J. O'Connell (1999)
Mol. Biol. Cell 10, 2905-2918
   Abstract »    Full Text »
A Fission Yeast Gene, him1+/dfp1+, Encoding a Regulatory Subunit for Hsk1 Kinase, Plays Essential Roles in S-Phase Initiation as Well as in S-Phase Checkpoint Control and Recovery from DNA Damage.
T. Takeda, K. Ogino, E. Matsui, M. K. Cho, H. Kumagai, T. Miyake, K.-i. Arai, and H. Masai (1999)
Mol. Cell. Biol. 19, 5535-5547
   Abstract »    Full Text »    PDF »


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