Crystal structure of a G : T/U mismatch-specific DNA glycosylase: Mismatch recognition by complementary-strand interactions

T. E. Barrett, R. Savva, G. Panayotou, T. Barlow, T. Brown, J. Jiricny and L. H. Pearl. Cell 92 (1), 117-129, 1998.

Abstract

G:U mismatches resulting from deamination of cytosine are the most common promutagenic lesions occurring in DNA. Uracil is removed in a base-excision repair pathway by uracil DNA-glycosylase (UDG), which excises uracil from both single- and double-stranded DNA. Recently, a biochemically distinct family of DNA repair enzymes has been identified, which excises both uracil and thymine, but only from mispairs with guanine. Crystal structures of the mismatch-specific uracil DNA-glycosylase (MUG) from E. coli, and of a DNA complex, reveal a remarkable structural and functional homology to UDGs despite low sequence identity. Details of the MUG structure explain its thymine DNA-glycosylase activity and the specificity for G:U/T mispairs, which derives from direct recognition of guanine on the complementary strand.