The ability to efficiently repair DNA damage and bypass the unrepaired lesions during DNA replication are two important means that confer cellular resistance to DNA damage. Oxidative base damage is primarily recognized by a variety of DNA glycosylases. It is becoming clear that the repair efficiency of a repair enzyme is affected by the sequence context that surrounds the base lesion, resulting in an apparent heterogeneity of repair by DNA glycosylases. Subsequent mutagenic bypass of unrepaired base lesions will lead to the observed mutation spectrum. The long-term goal of this project is to identify and characterize novel repair glycosylases that recognize and remove ROS-induced base lesions. In addition, the effect of sequence context that surrounds an individual base lesion on the efficiency of lesion repair and lesion bypass will also be elucidated. A thorough understanding of the effect of sequence context on lesion repair bypass will provide insightful clues to understand the mechanism involved in the generation of mutational spectra and hot spots.