The Saccharomyces cerevisiae RAD9, RAD17 and RAD24 genes are required for suppression of mutagenic post-replicative repair during chronic DNA damage.
In Saccharomyces cerevisiae, a DNA damage checkpoint in the S-phase is responsible for delaying DNA replication in response to genotoxic stress. This pathway is partially regulated by the checkpoint proteins Rad9, Rad17 and Rad24. Here, we describe a novel hypermutable phenotype for rad9Delta, rad17Delta and rad24Delta cells in response to a chronic 0.01% dose of the DNA alkylating agent MMS. We report that this hypermutability results from DNA damage introduction during the S-phase and is dependent on a functional translesion synthesis pathway. In addition, we performed a genetic screen for interactions with rad9Delta that confer sensitivity to 0.01% MMS. We report and quantify 25 genetic interactions with rad9Delta, many of which involve the post-replication repair machinery. From these data, we conclude that defects in S-phase checkpoint regulation lead to increased reliance on mutagenic translesion synthesis, and we describe a novel role for members of the S-phase DNA damage checkpoint in suppressing mutagenic post-replicative repair in response to sublethal MMS treatment.
Murakami-Sekimata
Akiko
A
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Huang
Dongqing
D
Piening
Brian D
BD
Bangur
Chaitanya
C
Paulovich
Amanda G
AG
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D013489:Suppression, Genetic
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C501395:RAD17 protein, S cerevisiae; C088385:RAD24 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C069930:rad9 protein
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