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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2003-6-24
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pubmed:databankReference |
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pubmed:abstractText |
Cytosine deamination is a major promutagenic process, generating G:U mismatches that can cause transition mutations if not repaired. Uracil is also introduced into DNA via nonmutagenic incorporation of dUTP during replication. In bacteria, uracil is excised by uracil-DNA glycosylases (UDG) related to E. coli UNG, and UNG homologs are found in mammals and viruses. Ung knockout mice display no increase in mutation frequency due to a second UDG activity, SMUG1, which is specialized for antimutational uracil excision in mammalian cells. Remarkably, SMUG1 also excises the oxidation-damage product 5-hydroxymethyluracil (HmU), but like UNG is inactive against thymine (5-methyluracil), a chemical substructure of HmU. We have solved the crystal structure of SMUG1 complexed with DNA and base-excision products. This structure indicates a more invasive interaction with dsDNA than observed with other UDGs and reveals an elegant water displacement/replacement mechanism that allows SMUG1 to exclude thymine from its active site while accepting HmU.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5-hydroxymethyluracil,
http://linkedlifedata.com/resource/pubmed/chemical/Cytosine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Glycosylases,
http://linkedlifedata.com/resource/pubmed/chemical/N-Glycosyl Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Pentoxyl,
http://linkedlifedata.com/resource/pubmed/chemical/SMUG1 protein, Xenopus laevis,
http://linkedlifedata.com/resource/pubmed/chemical/SMUG1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Uracil-DNA Glycosidase,
http://linkedlifedata.com/resource/pubmed/chemical/Xenopus Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1647-59
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12820976-Amino Acid Sequence,
pubmed-meshheading:12820976-Animals,
pubmed-meshheading:12820976-Base Pair Mismatch,
pubmed-meshheading:12820976-Base Pairing,
pubmed-meshheading:12820976-Base Sequence,
pubmed-meshheading:12820976-Cytosine,
pubmed-meshheading:12820976-DNA Damage,
pubmed-meshheading:12820976-DNA Glycosylases,
pubmed-meshheading:12820976-DNA Repair,
pubmed-meshheading:12820976-Humans,
pubmed-meshheading:12820976-Mice,
pubmed-meshheading:12820976-Mice, Knockout,
pubmed-meshheading:12820976-Models, Molecular,
pubmed-meshheading:12820976-Molecular Sequence Data,
pubmed-meshheading:12820976-Molecular Structure,
pubmed-meshheading:12820976-Mutation,
pubmed-meshheading:12820976-N-Glycosyl Hydrolases,
pubmed-meshheading:12820976-Pentoxyl,
pubmed-meshheading:12820976-Protein Conformation,
pubmed-meshheading:12820976-Sequence Homology, Amino Acid,
pubmed-meshheading:12820976-Substrate Specificity,
pubmed-meshheading:12820976-Uracil-DNA Glycosidase,
pubmed-meshheading:12820976-Xenopus Proteins,
pubmed-meshheading:12820976-Xenopus laevis
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pubmed:year |
2003
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pubmed:articleTitle |
Structure and specificity of the vertebrate anti-mutator uracil-DNA glycosylase SMUG1.
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pubmed:affiliation |
Cancer Research UK DNA Repair Enzyme Group, Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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