Interrogation, recognition and repair of damaged bases in DNA

BIOL 1

Gregory L. Verdine, gregory_verdine@harvard.edu, Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138
The bases in DNA are subject to attack by a wide variety of endogenous and exogenous agents. The resulting products cause mutations to occur during DNA replications and are therefore genotoxic. Repair of these lesions takes place by the base-excision DNA repair pathway, the central components of which are DNA glycosylases. These enzymes cleave the glycosidic bond linking the damaged base to the DNA backbone. Studies in our lab are focused on understanding how DNA glycosylases interrogate up to 10 million normal DNA bases in order to locate just one damaged base, and on understanding the mechanism by which DNA glycosylases catalyze the excision of damaged bases upon locating them. Recent progress on these fronts will be discussed.