New Family of Deamination Repair Enzymes in Uracil-DNA Glycosylase Superfamily*

@article{Lee2011NewFO,
  title={New Family of Deamination Repair Enzymes in Uracil-DNA Glycosylase Superfamily*},
  author={Hyun-wook Lee and Brian N. Dominy and Weiguo Cao},
  journal={The Journal of Biological Chemistry},
  year={2011},
  volume={286},
  pages={31282 - 31287}
}
DNA glycosylases play a major role in the repair of deaminated DNA damage. Previous investigations identified five families within the uracil-DNA glycosylase (UDG) superfamily. All enzymes within the superfamily studied thus far exhibit uracil-DNA glycosylase activity. Here we identify a new class of DNA glycosylases in the UDG superfamily that lacks UDG activity. Instead, these enzymes act as hypoxanthine-DNA glycosylases in vitro and in vivo. Molecular modeling and structure-guided mutational… 

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Endonuclease V: an unusual enzyme for repair of DNA deamination
  • Weiguo Cao
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TLDR
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References

SHOWING 1-10 OF 32 REFERENCES
Crystal structure of a thwarted mismatch glycosylase DNA repair complex
TLDR
The crystal structure of the Escherichia coli MUG enzyme complexed with an oligonucleotide containing a non‐hydrolysable deoxyuridine analogue mismatched with guanine is determined, providing the first structure of an intact substrate‐nucleotide productively bound to a hydrolytic DNA glycosylase.
Identification of Escherichia coli Mismatch-specific Uracil DNA Glycosylase as a Robust Xanthine DNA Glycosylase*
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.
Crystal structure of human thymine DNA glycosylase bound to DNA elucidates sequence-specific mismatch recognition
TLDR
The structure of hTDG reveals interactions that promote the stringent specificity for guanine versus adenine as the pairing partner of the target base and interactions that likely confer CpG sequence specificity.
The structural basis of specific base-excision repair by uracil–DNA glycosylase
TLDR
The 1.75-Å crystal structure of the uracil-DNA glycosylase from herpes simplex virus type-1 reveals a new fold, distantly related to dinucleotide-binding proteins, which suggests binding models for elongated single- and double-stranded DNA substrates.
Role of electrophilic and general base catalysis in the mechanism of Escherichia coli uracil DNA glycosylase.
TLDR
It is established by crystallography and heteronuclear NMR spectroscopy that the imidazole of His187 is neutral during the catalytic cycle of UDG, supporting a mechanism in which Asp64 serves as the general base and His187 acts as a neutral electrophile, stabilizing a developing negative charge on uracil O2 in the transition state.
An N-glycosidase from Escherichia coli that releases free uracil from DNA containing deaminated cytosine residues.
  • T. Lindahl
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1974
An enzyme that liberates uracil from single-stranded and double-stranded DNA containing deaminated cytosine residues and from deoxycytidylate-deoxyuridylate copolymers in the absence of Mg(++) has
...
...