A Dbf4 mutant contributes to bypassing the Rad53-mediated block of origins of replication in response to genotoxic stress |
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Authors: | Duch Alba Palou Gloria Jonsson Zophonias O Palou Roger Calvo Enrique Wohlschlegel James Quintana David G |
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Affiliation: | Biophysics Unit, Department of Biochemistry and Molecular Biology, School of Medicine, and Center for Biophysical Studies, Universitat Autonoma de Barcelona, 08193 Bellaterra, Catalonia, Spain. |
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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. |
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Keywords: | Cell Cycle Checkpoint Control Chromosomes DNA Damage DNA Replication |
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