Repair mechanisms for oxidative DNA damage

Reactive oxygen species are formed as by-products of mitochondrial aerobic respiration, as induced products upon exposure to certain environmental/exogenous agents (e.g. ionizing radiation), or as intended products during the immune response against invading foreign microbes. Although serving as essential signaling molecules in certain biological processes (e.g. during gene activation responses), these chemicals, particularly during oxidative stress when at excessive concentrations, can react with cellular components, most notably DNA, and in this capacity, promote mutagenesis or cell death, and in turn, human disease. We review here several of the common oxidative DNA damages as well as the DNA repair mechanisms related to maintaining genome integrity, and thus, preventing cancer formation and age-related disease. We focus mainly on participants of the base excision repair (BER) pathway. In brief, the steps of BER include: (a) excision of the damaged base, (b) incision of the DNA backbone at the apurinic/apyrimidinic (AP) site product, (c) removal of the AP terminal fragment, (d) gap-filling synthesis, and (e) ligation of the final nick.