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Checkpoint-Dependent Regulation of Origin Firing and Replication Fork Movement in Response to DNA Damage in Fission Yeast

Kumar, Sanjay and Huberman, Joel A. (2009) Checkpoint-Dependent Regulation of Origin Firing and Replication Fork Movement in Response to DNA Damage in Fission Yeast. Molecular and Cellular Biology, 29 (2). pp. 602-611. ISSN 0270-7306. PMCID PMC2612511. doi:10.1128/MCB.01319-08.

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To elucidate the checkpoint mechanism responsible for slowing passage through S phase when fission yeast cells are treated with the DNA-damaging agent methyl methanesulfonate (MMS), we carried out two-dimensional gel analyses of replication intermediates in cells synchronized by cdc10 block (in G1) followed by release into synchronous S phase. The results indicated that under these conditions early-firing centromeric origins were partially delayed but late-firing telomeric origins were not delayed. Replication intermediates persisted in MMS-treated cells, suggesting that replication fork movement was inhibited. These effects were dependent on the Cds1 checkpoint kinase and were abolished in cells overexpressing the Cdc25 phosphatase, suggesting a role for the Cdc2 cyclin-dependent kinase. We conclude that both partial inhibition of the firing of a subset of origins and inhibition of replication fork movement contribute to the slowing of S phase in MMS-treated fission yeast cells.

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Additional Information:© 2009, American Society for Microbiology. Received 19 August 2008/ Returned for modification 16 September 2008/ Accepted 30 October 2008. Published ahead of print on 10 November 2008. We thank Greg Freyer for the cdc10-v50 wild-type strain, and we thank the referees of both versions of the manuscript for their helpful comments. This work was supported by Public Health Service grants CA095908 from the National Cancer Institute and GM070566 from the National Institute for General Medical Sciences. This study benefited from Roswell Park Cancer Institute's Flow Cytometry facility, which is supported by Roswell Park Cancer Institute's Cancer Center support grant P30-CA16056 from the National Cancer Institute.
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Roswell Park Cancer InstituteUNSPECIFIED
Issue or Number:2
PubMed Central ID:PMC2612511
Record Number:CaltechAUTHORS:KUMmcb09
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ID Code:12958
Deposited By: Archive Administrator
Deposited On:11 Jan 2009 02:42
Last Modified:08 Nov 2021 22:34

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