Selected Publications

We are using mouse genetics to investigate the links between oxidative DNA damage and carcinogenesis, degenerative diseases, and aging.The damaged base, 8-oxoguanine, is a major mutagenic product of oxidative stress.Left unrepaired, 8-oxoguanine leads to G -T transversion mutations.To repair 8-oxoguanine the mammalian cell uses the DNA glycosylase Ogg1. The Ogg1 protein initiates DNA repair by removing 8-oxoguanine from DNA. The repair is then completed by the cell's general base excision repair pathway. In this pathway then, Ogg1is a component that specifically responds to oxidative damage. We have made transgenic mice that over-express the ogg1 gene and are making "knockout" mice for ogg1 as well.These strains of mice, and cells derived from them, will be used to probe the contribution of oxidative stress in tumorigenesis, aging, and tissue damage models.

Selected Publications

Rosenquist, T., Zharkov, D.O., and Grollman, A.P. (1997). Cloning and Characterization of a Mammalian 8-oxoguanine DNA-glycosylase. Proc. Natl. Acad. Sci 94:7429-7434.