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Abstract
The SRS2 gene of Saccharomyces cerevisiae encoding a 3′→5′ DNA helicase is part of the postreplication repair pathway and functions to ensure proper repair of DNA damage arising during DNA replication through pathways that do not involve homologous recombination. Through a synthetic gene array analysis, genes that are essential when Srs2 is absent have been identified. Among these are MRC1, TOF1, and CSM3, which mediate the intra-S checkpoint response. srs2Δ mrc1Δ synthetic lethality is due to inappropriate recombination, as the lethality can be suppressed by genetic elimination of homologous recombination. srs2Δ mrc1Δ synthetic lethality is dependent on the role of Mrc1 in DNA replication but independent of the role of Mrc1 in a DNA damage checkpoint response. mrc1Δ, tof1Δ and csm3Δ mutants have sister chromatid cohesion defects, implicating sister chromatid cohesion established at the replication fork as an important factor in promoting repair of stalled replication forks through gap repair.
We thank S. Elledge for the gift of the mrc1-AQ strain and Grant Brown, Giordano Liberi and Chiara Lucca for comments on the manuscript. The technical assistance of Anastasiya Epshtein is gratefully acknowledged.
This work was supported by Public Health Service grant GM53738 from the National Institutes of Health (H.L.K.) and by grants from the Canadian Institute of Health Research, Genome Canada, and Genome Ontario (C.B.).