Checkpoint-Dependent Activation of Mutagenic Repair in Saccharomyces cerevisiae pol3-01 Mutants

• Published in: Molecular cell 2000-09, Vol.6 (3), p.593-603
• Main Authors: Datta, Abhijit, Schmeits, James L., Amin, Neelam S., Lau, Patrick J., Myung, Kyungjae, Kolodner, Richard D.
• Format: Article
• Language: English
• Subjects: 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; POL3 gene; Protein Kinases - genetics; Protein-Serine-Threonine Kinases; RAD6 gene; S Phase - genetics; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(00)00058-7

The Saccharomyces cerevisiae DNA polymerase δ 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.