Crystal Structure of a G:T/U Mismatch-Specific DNA Glycosylase Mismatch Recognition by Complementary-Strand Interactions

@article{Barrett1998CrystalSO,
  title={Crystal Structure of a G:T/U Mismatch-Specific DNA Glycosylase Mismatch Recognition by Complementary-Strand Interactions},
  author={Tracey E. Barrett and Renos Savva and George Panayotou and Tom Barlow and Tom Brown and Josef Jiricny and Laurence H. Pearl},
  journal={Cell},
  year={1998},
  volume={92},
  pages={117-129}
}
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… 
Structure and activity of a thermostable thymine-DNA glycosylase: evidence for base twisting to remove mismatched normal DNA bases.
TLDR
It is proposed that functionally significant differences exist in DNA repair enzyme extrahelical nucleotide binding and catalysis that are characteristic of whether the target base is damaged or is a normal base within a mispair.
Structure and function in the uracil-DNA glycosylase superfamily.
  • L. Pearl
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Deamination of cytosine to uracil is one of the major pro-mutagenic events in DNA, causing G:C-->A:T transition mutations if not repaired before replication. Repair of uracil-DNA is achieved in a
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TLDR
By DNA footprinting analysis, it is shown that MPG, but not UDG, bound to base-pair mismatches especially to less stable pyrimidine-pyrimidine pairs, without catalyzing detectable base cleavage.
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TLDR
Molecular modeling and molecular dynamics simulations reveal distinct hydrogen-bonding patterns in the active site of E. coli MUG that account for the specificity differences between MUG and human thymine DNA glycosylase as well as that between the wild type MUGand the Asn-140 and Ser-23 mutants.
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Structure of the uracil-DNA N-glycosylase (UNG) from Deinococcus radiodurans.
TLDR
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Specificity and Catalytic Mechanism in Family 5 Uracil DNA Glycosylase*
TLDR
Mutational analysis coupled with molecular modeling and molecular dynamics analysis reveals that although hydrogen bonding to O2 of uracil underlies the UDG activity in a dissociative fashion, Tth UDGb relies on multiple catalytic residues to facilitate its excision of hypoxanthine and xanthine.
Differential modes of DNA binding by mismatch uracil DNA glycosylase from Escherichia coli: implications for abasic lesion processing and enzyme communication in the base excision repair pathway
TLDR
This is the first report of cooperativity in the uracil DNA glycosylase superfamily of enzymes, and forms the basis of product inhibition in Mug, and provides a new perspective on abasic site protection.
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