Repair of oxidized DNA bases in the yeast Saccharomyces cerevisiae

Abstract

An essential requirement for all organisms is to maintain its genomic integrity. Failure to do so, in multicellular organisms such as man, can lead to degenerative pathologies such as cancer and aging. Indeed, a very low spontaneous mutation rate is observed in eukaryotes, suggesting either an inherent stability of the genome or efficient DNA repair mechanisms. In fact, DNA is subjected to unceasing attacks by a variety of endogenous and environmental reactive chemical species yielding a multiplicity of DNA damage, the deleterious action of which is counteracted by efficient repair enzymes. Reactive oxygen species formed in cell as by-products of normal metabolism are probably the major source of endogenous DNA damage. Amongst oxidative damage, base modifications constitute an important class of lesions whose lethal or mutagenic action has been established. Oxidatively damaged DNA bases are mostly repaired by the base excision repair pathway (BER) in prokaryotes and eukaryotes. However, the nucleotide excision repair pathway (NER) may also play a role in the repair of some oxidized bases in DNA. Here, we describe repair pathways implicated in the removal of oxidized bases in Saccharomyces cerevisiae. Yeast is a simple organism that can be used as a paradigm for DNA repair in all eukaryotic cells. S cerevisiae possesses three DNA glycosylases that catalyze the excision of oxidized bases from damaged DNA: the Ogg1, Ntg1 and Ntg2 proteins. The aim of this review is to summarize recent findings dealing with the formation, the biological consequences and the repair of oxidized DNA bases in S cerevisiae.