Checkpoint activation regulates mutagenic translesion synthesis.
Cells have evolved checkpoint responses to arrest or delay the cell cycle, activate DNA repair networks, or induce apoptosis after genomic perturbation. Cells have also evolved the translesion synthesis processes to tolerate genomic lesions by either error-free or error-prone repair. Here, we show that after a replication perturbation, cells exhibit a mutator phenotype, which can be significantly affected by mutations in the checkpoint elements Cds1 and Rad17 or translesion synthesis polymerases DinB and Polzeta. Cells respond to genomic perturbation by up-regulation of DinB in a checkpoint activation-dependent manner. Moreover, association of DinB with chromatin is dependent on functional Rad17, and DinB physically interacts with the checkpoint-clamp components Hus1 and Rad1. Thus, translesion synthesis is a part of the checkpoint response.
Kai
Mihoko
M
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305-5324, USA.
Wang
Teresa S-F
TS
D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D064447:Checkpoint Kinase 2; D002843:Chromatin / Q000378:metabolism; D004256:DNA Polymerase I / Q000235:genetics / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes; D004261:DNA Replication; D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000502:physiology; D004720:Endonucleases / Q000235:genetics / Q000502:physiology; D029968:Escherichia coli Proteins; D018816:Genes, cdc; D016296:Mutagenesis; D009687:Nuclear Proteins; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins
D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C094399:DinB protein, E coli; D029968:Escherichia coli Proteins; D009687:Nuclear Proteins; C501395:RAD17 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C106332:hus1 protein, S pombe; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578636:Cds1 protein, S pombe; D017346:Protein Serine-Threonine Kinases; C425929:DNA polymerase zeta; D004256:DNA Polymerase I; D004259:DNA-Directed DNA Polymerase; D004720:Endonucleases; C069266:RAD1 protein, S cerevisiae; D045643:DNA Repair Enzymes