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PMID: 12514100 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Checkpoint activation regulates mutagenic translesion synthesis.

Genes & development ·Vol. 17 ·No. 1 ·2003-01-01 ·Pages 64-76

Kai M, Wang TS

Abstract

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.

MeSH Terms
Bacterial Proteins/genetics,physiology Cell Cycle/genetics,physiology Cell Cycle Proteins/genetics,physiology Checkpoint Kinase 2 Chromatin/metabolism DNA Polymerase I/genetics,physiology DNA Repair/physiology DNA Repair Enzymes DNA Replication DNA-Binding Proteins DNA-Directed DNA Polymerase/genetics,physiology Endonucleases/genetics,physiology Escherichia coli Proteins Genes, cdc Mutagenesis Nuclear Proteins Protein Kinases/genetics,physiology Protein Serine-Threonine Kinases Saccharomyces cerevisiae/cytology,genetics Saccharomyces cerevisiae Proteins/genetics,physiology Schizosaccharomyces pombe Proteins
Chemicals
Bacterial Proteins Cell Cycle Proteins Chromatin DNA-Binding Proteins DinB protein, E coli Escherichia coli Proteins Nuclear Proteins RAD17 protein, S cerevisiae Saccharomyces cerevisiae Proteins Schizosaccharomyces pombe Proteins hus1 protein, S pombe Protein Kinases Checkpoint Kinase 2 Cds1 protein, S pombe Protein Serine-Threonine Kinases DNA polymerase zeta DNA Polymerase I DNA-Directed DNA Polymerase Endonucleases RAD1 protein, S cerevisiae DNA Repair Enzymes
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kai Mihoko
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305-5324, USA.
Wang Teresa S-F
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1043203
Published
2003-01-01
Pages
64-76
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC195967
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.1043203 PMC Full Text View journal details
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