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

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 (H 2 O 2 ) 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 H 2 O 2 concentrations (5–100 m M for 20 min), followed by catalase treatment (500 IU/ml). In these conditions, the ogg1 mutant was more sensitive than the WT strain to H 2 O 2 (concentration 40–60 m M ). Unexpectedly, the inactivation of NTG2 in an ogg1 background was able to suppress both sensitivity and mutagenesis induced by H 2 O 2 . Indeed, even the ntg2 single mutant was more resistant than the WT (60–100 m M H 2 O 2 ). 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 H 2 O 2 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 H 2 O 2 and their relationships with iron and copper ions are discussed. Copyright © 2004 John Wiley & Sons, Ltd.