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Originally published as MBoC in Press, 10.1091/mbc.E08-08-0798 on November 26, 2008

Vol. 20, Issue 3, 819-833, February 1, 2009

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Mus81, Rhp51(Rad51), and Rqh1 Form an Epistatic Pathway Required for the S-Phase DNA Damage Checkpoint

Nicholas Willis, and Nicholas Rhind

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605

Submitted August 5, 2008; Revised October 20, 2008; Accepted November 19, 2008
Monitoring Editor: Orna Cohen-Fix

The S-phase DNA damage checkpoint slows the rate of DNA synthesis in response to damage during replication. In the fission yeast Schizosaccharomyces pombe, Cds1, the S-phase-specific checkpoint effector kinase, is required for checkpoint signaling and replication slowing; upon treatment with the alkylating agent methyl methane sulfonate, cds1{Delta} mutants display a complete checkpoint defect. We have identified proteins downstream of Cds1 required for checkpoint-dependant slowing, including the structure-specific endonuclease Mus81 and the helicase Rqh1, which are implicated in replication fork stability and the negative regulation of recombination. Removing Rhp51, the Rad51 recombinase homologue, suppresses the slowing defect of rqh1{Delta} mutants, but not that of mus81{Delta} mutant, defining an epistatic pathway in which mus81 is epistatic to rhp51 and rhp51 is epistatic to rqh1. We propose that restraining recombination is required for the slowing of replication in response to DNA damage.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-08-0798) on November 26, 2008.

Address correspondence to: Nicholas Rhind (nick.rhind{at}umassmed.edu)

Abbreviations used: IR, ionizing radiation; MMS, methyl methane sulfonate.




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