The molecular genetics and enzymology of DNA excision repair are the long standing interests of this laboratory. It is now well established that defects in DNA repair predispose to cancer. We study DNA repair enzymes termed DNA glycosylases which recognize oxidatively damaged bases in DNA and remove them. Such damaged bases may be formed as a consequence of exposure to ionizing and ultraviolet radiation as well as other oxygen radical-mediated stresses. We hypothesize that these enzymes function as tumor suppressor genes by minimizing the spontaneous mutation rate. Recently, we isolated and sequenced the cDNA of one such human repair enzyme demonstrating that the protein structure of this enzyme is highly conserved throughout all biological domains. By constructing "knock out" mice lacking this and other repair enzymes, we will be able to better assess their role in maintaining genomic integrity and preventing the development of cancer.