This project proposes to investigate the repair of a particular DNA lesion induced by reactive oxygen species-induced oxidative damage, and investigate a possible link between oxygen free radical-induced mutagenesis and human cancer. The objective of this project is to identify and characterize the function of a cellular system dedicated to the repair of 5-hydroxy-2'-deoxycytidine (5-OHdC), a stable and potentially mutagenic product of oxidative damage to cytidine. This will be accomplished through the use of a double-stranded DNA template which contains a single 5-OHdC lesion at a specified site as a substrate for specific repair of 5-OHdC. Furthermore, the possibility that deficiencies in the repair of this oxidative lesion may be linked to carcinogenesis will be investigated by characterizing the repair of 5-OHdC in a human hereditary disorder characterized by hypersensitivity to oxygen.
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