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

Journal article

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.

Authors: Barrett, T; Savva, R; Panayotou, G; Barlow, T; Brown, T

• Publication status: Published
• Journal: Cell
• Volume: 92
• Issue: 1
• Pages: 117-129
• Publication date: 1998-01-01
• DOI: 10.1016/s0092-8674(00)80904-6
• EISSN: 1097-4172
• ISSN: 0092-8674
• Language: English
• Keywords: DNA; Viral Proteins; DNA, Complementary; DNA Damage; Molecular Sequence Data; Uracil-DNA Glycosidase; Protein Binding; N-Glycosyl Hydrolases; Endodeoxyribonucleases; Crystallography, X-Ray; Catalysis; DNA Repair; DNA Glycosylases; Sequence Homology, Amino Acid; Deoxyribonuclease (Pyrimidine Dimer); Substrate Specificity; Crystallization; Escherichia coli; Nucleic Acid Heteroduplexes; Amino Acid Sequence