Genetic control of mutagenesis by the base analog 6-N-hydroxylaminopurine (HAP) was studied in a set of isogenic yeast strains carrying null or point mutations in DNA repair and replication genes. Null alleles of the PMS1, RAD6, REV3 and RAD52 genes did not affect HAP mutagenesis. Defects in 3'-> 5' exonucleases associated with DNA polymerases ε and δ led to 2- to 3-fold increases in HAP-induced forward Can(r) mutant frequency. A similar increase was observed for FOA(r) mutants but only in the strain with a defective exonuclease of the polymerase ε (mutation pol2-4). The polymerase ε mutations, pol2-9 and pol2-18, which lead to temperature-sensitivity, and pol2-1 (insertion of URA3 at the position coding for amino acid 1134 in the POL2 gene) substantially reduced HAP mutagenesis. The polymerase δ mutation, cdc2-2, slightly reduced HAP mutagenesis. Enhanced proofreading was not the cause of the antimutator effect in the pol2-18 bearing strain, inasmuch as antimutator effect was observed in the pol2-4,18 mutant strain lacking proofreading. From the data obtained, we conclude that both DNA polymerase ε and δ participate in mutation generation by KAP.
- Base analog 6-N-hydroxylaminopurine
- DNA polymerase
- DNA replication
- Exonucleolytic proofreading
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