Choreography of oxidative damage repair in mammalian genomes.

The lesions induced by reactive oxygen species in both nuclear and mitochondrial genomes include altered bases, abasic (AP) sites, and single-strand breaks, all repaired primarily via the base excision repair (BER) pathway. Although the basic BER process (consisting of five sequential steps) could be reconstituted in vitro with only four enzymes, it is now evident that repair of oxidative damage, at least in mammalian cell nuclei, is more complex, and involves a number of additional proteins, including transcription- and replication-associated factors. These proteins may be required in sequential repair steps in concert with other cellular changes, starting with nuclear targeting of the early repair enzymes in response to oxidative stress, facilitation of lesion recognition, and access by chromatin unfolding via histone acetylation, and formation of metastable complexes of repair enzymes and other accessory proteins.

Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA.

8-oxoguanine (8-oxoG), ring-opened purines (formamidopyrimidines or Fapys), and other oxidized DNA base lesions generated by reactive oxygen species are often mutagenic and toxic, and have been implicated in the etiology of many diseases, including cancer, and in aging. Repair of these lesions in all organisms occurs primarily via the DNA base excision repair pathway, initiated with their excision by DNA glycosylase/AP lyases, which are of two classes. One class utilizes an internal Lys residue as the active site nucleophile, and includes Escherichia coli Nth and both known mammalian DNA glycosylase/AP lyases, namely, OGG1 and NTH1.