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J. Biol. Chem., Vol. 279, Issue 42, 43574-43580, October 15, 2004

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On the Slowing of S Phase in Response to DNA Damage in Fission Yeast^*

Sanjay Kumar and Joel A. Huberman

From the Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263

Eukaryotic cells slow their progression through S phase upon DNA damage. The mechanism that leads to this slowing is called the intra-S-phase checkpoint. Previous studies demonstrated that in the fission yeast Schizosaccharomyces pombe this checkpoint is mediated by a pathway that includes Rad3 (similar to human ATR and ATM) and Cds1 (similar to human Chk1 and Chk2). Here we present evidence that a major downstream target of this pathway is the cyclin-dependent kinase, Cdc2. We also present evidence suggesting that the intra-S-phase checkpoint makes a relatively minor contribution to the survival of cells with damaged DNA.

Received for publication, July 12, 2004 , and in revised form, August 4, 2004.

^* This work was supported by National Institutes of Health Grants GM49294, CA84302, and CA95908. These studies benefited from Roswell Park Cancer Institute's Flow Cytometry and Biopolymer facilities, which are supported by Roswell Park Cancer Institute's Cancer Center Support Grant P30CA16056 from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 716-845-3047; Fax: 716-845-8126; E-mail: huberman{at}buffalo.edu.

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