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A Dbf4 mutant contributes to bypassing the Rad53-mediated block of origins of replication in response to genotoxic stress.

Duch A, Palou G, Jonsson ZO, Palou R, Calvo E, Wohlschlegel J, Quintana DG
The Journal of biological chemistry


An intra-S phase checkpoint slows the rate of DNA replication in response to DNA damage and replication fork blocks in eukaryotic cells. In the budding yeast Saccharomyces cerevisiae, such down-regulation is achieved through the Rad53 kinase-dependent block of origins of replication. We have identified the Rad53 phosphorylation sites on Dbf4, the activator subunit of the essential S phase Dbf4-dependent kinase, and generated a non-phosphorylatable Dbf4 mutant (dbf4(7A)). We show here that dbf4(7A) is a bona fide intra-S phase checkpoint bypass allele that contributes to abrogating the Rad53 block of origin firing in response to genotoxic stress.

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