Checkpoint-dependent activation of mutagenic repair in Saccharomyces cerevisiae pol3-01 mutants

Mol Cell. 2000 Sep;6(3):593-603. doi: 10.1016/s1097-2765(00)00058-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cell Cycle Proteins*
  • DNA Polymerase III / genetics*
  • DNA Polymerase III / metabolism
  • DNA Repair / genetics*
  • DNA Replication / genetics
  • Frameshift Mutation
  • Fungal Proteins / genetics
  • Gene Deletion
  • Genotype
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • Phenotype
  • Protein Kinases / genetics
  • Protein-Serine-Threonine Kinases
  • S Phase / genetics
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins*

Substances

  • Cell Cycle Proteins
  • Fungal Proteins
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • DUN1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • DNA Polymerase III