Annu. Rev. Biophys. Biomol. Struct. 1999. 28:101–28 Copyright c  1999 by Annual Reviews. All rights reserved DNA REPAIR MECHANISMS FOR THE RECOGNITION AND REMOVAL OF DAMAGED DNA BASES Clifford D. Mol, Sudip S. Parikh, Christopher D. Putnam, Terence P. Lo, and John A. Tainer Department of Molecular Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037; e-mail: jat@scripps.edu KEY WORDS: DNA base excision repair, DNA glycosylases, minor groove recognition, nucleotide flipping ABSTRACT Recent structural and biochemical studies have begun to illuminate how cells solve the problems of recognizing and removing damaged DNA bases. Bases damaged by environmental, chemical, or enzymatic mechanisms must be efficiently found within a large excess of undamaged DNA. Structural studies suggest that a rapid damage-scanning mechanism probes for both conformational deviations and local deformability of the DNA base stack. At susceptible lesions, enzyme-induced conformational changes lead to direct interactions with specific damaged bases. The diverse array of damaged DNA bases are processed through a two-stage pathway in which damage-specific enzymes recognize and remove the base lesion, creating a common abasic site intermediate that is processed by damage-general repair enzymes to restore the correct DNA sequence. CONTENTS PERSPECTIVES AND OVERVIEW ............................................ 102 DEAMINATION ............................................................ 104 Uracil-DNA Glycosylase ................................................... 104 G·T/U Mismatch-Specific DNA Glycosylase .................................... 108 OXIDATION ................................................................ 110 MutY Mismatched-Adenine Glycosylase ....................................... 110 101 1056-8700/99/0610-0101$08.00 Annu. Rev. Biophys. Biomol. Struct. 1999.28:101-128. Downloaded from www.annualreviews.org Access provided by University of California - Berkeley on 12/19/14. For personal use only.