Checkpoint-dependent activation of mutagenic repair in Saccharomyces cerevisiae pol3-01 mutants.
The Saccharomyces cerevisiae DNA polymerase delta proofreading exonuclease-defective mutation pol3-01 is known to cause high rates of accumulating mutations. The pol3-01 mutant was found to have abnormal cell cycle progression due to activation of the S phase checkpoint. Inactivation of the S phase checkpoint suppressed both the pol3-01 cell cycle progression defect and mutator phenotype, indicating that the pol3-01 mutator phenotype was dependent on the S phase damage checkpoint pathway. Epistasis analysis suggested that a portion of the pol3-01 mutator phenotype involves members of the RAD6 epistasis group that function in both error-free and error-prone repair. These results indicate that activation of a checkpoint in response to certain types of replicative defects can result in the accumulation of mutations.
Datta
A
A
Ludwig Institute for Cancer Research, University of California, San Diego, Medical School, La Jolla 92093, USA.
Schmeits
J L
JL
Amin
N S
NS
Lau
P J
PJ
Myung
K
K
Kolodner
R D
RD
D001483:Base Sequence; D018797:Cell Cycle Proteins; D004258:DNA Polymerase III / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D016368:Frameshift Mutation; D005656:Fungal Proteins / Q000235:genetics; D017353:Gene Deletion; D005838:Genotype; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D016196:S Phase / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C104169:DUN1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D004258:DNA Polymerase III