Role of OGG1 and NTG2 in the repair of oxidative DNA damage and mutagenesis induced by hydrogen peroxide in Saccharomyces cerevisiae: relationships with transition metals iron and copper

摘要

The base excision repair pathway of Saccharomyces cerevisiae possesses three DNA N-glycosylases, viz. Ogg1p, Ngt1p and Ntg2p, involved in the repair of oxidative DNA damage. It was previously reported that inactivation of any of these activities, in most cases, did not generate a sensitive mutant phenotype to a variety of oxidative agents. Only the ntg1 mutant appeared to be more sensitive to hydrogen peroxide (H2O2) than a wild-type (WT) strain. In the present study we evaluated the role of S. cerevisiae OGG1 and NTG2 genes in the repair of oxidative lesions induced by high H2O2 concentrations (5-100 mM for 20 min), followed by catalase treatment (500 IU/ml). In these conditions, the ogg1 mutant was more sensitive than the WT strain to H2O2 (concentration 40-60 mM). Unexpectedly, the inactivation of NTG2 in an ogg1 background was able to suppress both sensitivity and mutagenesis induced by H2O2. Indeed, even the ntg2 single mutant was more resistant than the WT (60-100 mM H2O2). The use of metal ion chelators dipyridyl and neocuproine allowed us to evaluate the participation of iron and copper ions in the production of lethal and mutagenic lesions during H2O2 treatment in different DNA repair-deficient S. cerevisiae strains. The roles of OGG1 and NTG2 genes in the repair of lethal and mutagenic oxidative lesions induced by H2O2 and their relationships with iron and copper ions are discussed.