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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.
PREFACE; 1. 1. Overview; MICHAEL P. STONE; 2. 2. Structural Consequences of Epimerization of Thymine Glycol Lesions in Duplex DNA: Implications for DNA Repair; KYLE L. BROWN, MARINA ROGINSKAYA, YUE ZOU, ALVIN ALTAMIRANO, ASHIS K. BASU, AND MICHAEL P. STONE; 3. 3. Structural Studies of Alkylpurine DNA Glycosylases; EMILY H. RUBINSON, SURAJ ADHIKARY, AND BRANDT F. EICHMAN; 4. 4. Dynamics in Uracil Base Excision Repair; JOSHUA I. FRIEDMAN AND JAMES T. STIVERS; 5. 5. Biochemical and Structural Domain Analysis of Xeroderma Pigmentosum Complementation Group C Protein; STEVEN M. SHELL AND WALTER J. CHAZIN; 6. 6. Effects of Sequence Context on O6-Alkylguanine DNA Alkyltransferase Repair of O6-Alkyl-Deoxyguanosine Adducts; REBECCA GUZA, ANTHONY E. PEGG, AND NATALIA TRETYAKOVA; 7. 7. Impact of Carcinogen-DNA Adducts on DNA Methylation; ELIZAVETA S. GROMOVA, OKSANA M. SUBACH, VLADIMIR B. BASKUNOV, AND NICHOLAS E. GEACINTOV; INDEXES; AUTHOR INDEX; SUBJECT INDEX