Inactivation of Saccharomyces cerevisiae OGG1 DNA repair gene leads to an increased frequency of mitochondrial mutants

The OGG1 gene encodes a highly conserved DNA glycosylase that repairs oxidi zed guanines in DNA, We have investigated the in vivo function of the Ogg1 protein in yeast mitochondria, We demonstrate that inactivation of ogg1 lea ds to at least a 2-fold increase in production of spontaneous mitochondrial mutants compared with wild-type, Using green fluorescent protein (GFP) we show that a GFP-Ogg1 fusion protein is transported to mitochondria, However , deletion of the first 11 amino acids from the N-terminus abolishes the tr ansport of the GFP-Ogg1 fusion protein into the mitochondria. This analysis indicates that the N-terminus of Ogg1 contains the mitochondrial localizat ion signal, We provide evidence that both yeast and human Ogg1 proteins pro tect the mitochondrial genome from spontaneous, as well as induced, oxidati ve damage. Genetic analyses revealed that the combined inactivation of OGG1 and OGG2 [encoding an isoform of the Ogg1 protein, also known as endonucle ase three-like glycosylase (Ntg1)] leads to suppression of spontaneously ar ising mutations in the mitochondrial genome when compared with the ogg1 sin gle mutant or the wildtype, Together, these studies provide in vivo evidenc e for the repair of oxidative lesions in the mitochondrial genome by human and yeast Ogg1 proteins. Our study also identifies Ogg2 as a suppressor of oxidative mutagenesis in mitochondria.