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

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



Life Sciences | Medicine and Health Sciences


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 MMS, cds1Delta 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 homolog, suppresses the slowing defect of rqh1Delta mutants, but not that of mus81Delta 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.

DOI of Published Version



Mol Biol Cell. 2008 Nov 26. Link to article on publisher's site

Journal/Book/Conference Title

Molecular biology of the cell

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Link to Article in PubMed

PubMed ID