Structural highlights
Function
[SMUG1_XENLA] Responsible for recognizing base lesions in the genome and initiating base excision DNA repair. Acts as a monofunctional DNA glycosylase specific for uracil (U) residues in DNA and has a preference for single-stranded DNA substrates. No enzymatic activity towards G/T mismatches.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structure and specificity of the vertebrate anti-mutator uracil-DNA glycosylase SMUG1.,Wibley JE, Waters TR, Haushalter K, Verdine GL, Pearl LH Mol Cell. 2003 Jun;11(6):1647-59. PMID:12820976[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wibley JE, Waters TR, Haushalter K, Verdine GL, Pearl LH. Structure and specificity of the vertebrate anti-mutator uracil-DNA glycosylase SMUG1. Mol Cell. 2003 Jun;11(6):1647-59. PMID:12820976
