CRYSTAL-STRUCTURE OF A G-T U MISMATCH-SPECIFIC DNA GLYCOSYLASE - MISMATCH RECOGNITION BY COMPLEMENTARY-STRAND INTERACTIONS/

G:U mismatches resulting from deamination of cytosine are the most com mon promutagenic lesions occurring in DNA. Uracil is removed in a base -excision repair pathway by uracil DNA-glycosylase (UDG), which excise s uracil from both single-and double-stranded DNA. Recently, a biochem ically distinct family of DNA repair enzymes has been identified, whic h 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 structura l and functional homology to UDGs despite low sequence identity. Detai ls of the MUG structure explain its thymine DNA-glycosylase activity a nd the specificity for G:U/T mispairs, which derives from direct recog nition of guanine on the complementary strand.