Contribution of base excision repair, nucleotide excision repair, and DNA recombination to alkylation resistance of the fission yeast Schizosaccharomyces pombe

DNA damage is unavoidable, and organisms across the evolutionary spectrum p ossess DNA repair pathways that are critical for cell viability and genomic stability. To understand the role of base excision repair (BER) in protect ing eukaryotic cells against alkylating agents, we generated Schizosaccharo myces pombe pombe strains mutant for the mag13-methyladenine DNA glycosylas e gene. We report that S. pombe mag1 mutants have only a slightly increased sensitivity to methylation damage, suggesting that Mag1-initiated BER play s a surprisingly minor role in alkylation resistance in this organism. We g o on to show that other DNA repair pathways play a larger role than BER in alkylation resistance. Mutations in genes involved in nucleotide excision r epair (rad13) and recombinational repair (rhp51) are much more alkylation s ensitive than mag1 mutants. In addition, S. pombe mutant for the flap endon uclease rad2 gene, whose precise function in DNA repair is unclear, were al so more alkylation sensitive than mag1 mutants. Further, mag1 and rad13 int eract synergistically for alkylation resistance, and mag1 and rhp51 display a surprisingly complex genetic interaction. A model for the role of DER in the generation of alkylation-induced DNA strand breaks in S. pombe is disc ussed.