Structural Biology of DNA Damage and Repair

The human genome is continuously exposed to many classes of genotoxins. Of these, three that will be discussed herein include 5,6-dihydroxy-5,6- dihydrothymine (thymine glycol; Tg), O6-methylguanine (O6MeG), and benzo[a]pyrene. In all cases, if the genome is not repaired, these and other genotoxic lesions precipitate serious biological consequences, including altered gene expression, mutation, and cell death. In addition to the genotoxic responses, it is increasingly being recognized that DNA lesions can alter the epigenetic profiles that are imprinted by naturally occurring DNA modifications. The impetus for this volume came from a recent symposium sponsored by the ACS Division of Chemical Toxicology, bringing together scientists interested in the synthesis and structures of site-specific DNA adducts and in mechanistic aspects of DNA repair. This volume presents work at the interface between the structural biology of DNA damage and DNA repair.