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

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2008 Nov 13

PMID 19001087

Citations 15

Authors

Sanjay Kumar

Joel A Huberman

Affiliations

Soon will be listed here.

Abstract

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 G(1)) 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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