title: 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.
authors.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.
authors.forename: Alba
authors.initials: A
authors.lastname: Duch
authors.forename: Gloria
authors.initials: G
authors.lastname: Palou
authors.forename: Zophonias O
authors.initials: ZO
authors.lastname: Jonsson
authors.forename: Roger
authors.initials: R
authors.lastname: Palou
authors.forename: Enrique
authors.initials: E
authors.lastname: Calvo
authors.forename: James
authors.initials: J
authors.lastname: Wohlschlegel
authors.forename: David G
authors.initials: DG
authors.lastname: Quintana
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D018741:Replication Origin; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004271:DNA, Fungal; C088096:Dbf4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae