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

Barrett TE, Savva R, Panayotou G, Barlow T, Brown T, Jiricny J, Pearl LH

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.

Keywords:

Escherichia coli

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DNA Damage

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DNA Glycosylases

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Endodeoxyribonucleases

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Deoxyribonuclease (Pyrimidine Dimer)

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N-Glycosyl Hydrolases

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Viral Proteins

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DNA

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DNA, Complementary

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Nucleic Acid Heteroduplexes

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Crystallization

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Crystallography, X-Ray

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DNA Repair

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Amino Acid Sequence

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Protein Binding

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Sequence Homology, Amino Acid

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Substrate Specificity

,

Catalysis

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Molecular Sequence Data

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Uracil-DNA Glycosidase