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

ABSTRACT: 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.

SUBMITTER: Duch A

PROVIDER: S-EPMC3024743 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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

Duch Alba A Palou Gloria G Jonsson Zophonias O ZO Palou Roger R Calvo Enrique E Wohlschlegel James J Quintana David G DG

The Journal of biological chemistry 20101123 4

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(7 ...[more]

PMID: 21098477

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