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 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.
Barrett
T E
TE
Department of Biochemistry and Molecular Biology, University College London, United Kingdom.
Savva
R
R
Panayotou
G
G
Barlow
T
T
Brown
T
T
Jiricny
J
J
Pearl
L H
LH
D000595:Amino Acid Sequence; D002384:Catalysis; D003460:Crystallization; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D045647:DNA Glycosylases; D004260:DNA Repair; D018076:DNA, Complementary / Q000737:chemistry / Q000378:metabolism; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D051981:Uracil-DNA Glycosidase; D014764:Viral Proteins / Q000494:pharmacology
D018076:DNA, Complementary; D009692:Nucleic Acid Heteroduplexes; D014764:Viral Proteins; C027619:uracil-DNA glycosylase inhibitor protein, B. subtilis bacteriophage; D004247:DNA; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase