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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Catalysis
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Crystallization
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Crystallography, X-Ray
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DNA / chemistry
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DNA / metabolism
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DNA Damage
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DNA Glycosylases*
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DNA Repair
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DNA, Complementary / chemistry
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DNA, Complementary / metabolism
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Deoxyribonuclease (Pyrimidine Dimer)
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Endodeoxyribonucleases / chemistry
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Endodeoxyribonucleases / metabolism
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Escherichia coli / chemistry
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Escherichia coli / enzymology
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Molecular Sequence Data
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N-Glycosyl Hydrolases / antagonists & inhibitors
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N-Glycosyl Hydrolases / chemistry*
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N-Glycosyl Hydrolases / metabolism
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Nucleic Acid Heteroduplexes / chemistry
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Protein Binding
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Sequence Homology, Amino Acid
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Substrate Specificity
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Uracil-DNA Glycosidase
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Viral Proteins / pharmacology
Substances
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DNA, Complementary
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Nucleic Acid Heteroduplexes
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Viral Proteins
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uracil-DNA glycosylase inhibitor protein, B. subtilis bacteriophage
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DNA
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Endodeoxyribonucleases
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Deoxyribonuclease (Pyrimidine Dimer)
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DNA Glycosylases
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N-Glycosyl Hydrolases
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Uracil-DNA Glycosidase