Oxidative stress in the cell leads to guanine oxidation, a phenomenon that underlies age-related disorders including cancer, neurological and vascular diseases. Although the formation of 8-oxoguanosine (OG) has been known for some time, our laboratory has uncovered the structures and mechanisms of formation of several of the additional oxidation products, many of which are much more mutagenic than OG. In this work, funded by the National Cancer Institute, we examine the cellular conditions leading to various oxidized lesions and the behavior of DNA containing these lesions with DNA processing enzymes including polymerases and repair enzymes.
Funding: NIH R01 CA090689
Collaborators: Sheila David (UC Davis), Susan Wallace (U. Vermont), Sylvie Doublié (U. Vermont) and Magnar Bjørås (Oslo University)