Uracil DNA glycosylase family 3 subfamily, includes single-strand-selective monofunctional uracil-DNA glycosylase 1 and similar proteins
Uracil DNA glycosylase family 3 includes Human SMUG1 that can remove uracil and its oxidized pyrimidine derivatives from both, single-stranded DNA and double-stranded DNA, with a preference for single-stranded DNA substrates. The SMUG-targeted mismatched uracil derivatives include 5-hydroxyuracil, 5-hydroxymethyluracil and 5-formyluracil. Also included in this subfamily is Geobacter metallireducens SMUG1 which has dual substrate specificities for DNA with uracil or xanthine. UDG catalyzes the removal of uracil from DNA to initiate the DNA base excision repair pathway. Uracil in DNA can arise as a result of mis-incorporation of dUMP residues by DNA polymerase or deamination of cytosine. Uracil mispaired with guanine in DNA is one of the major pro-mutagenic events, causing G:C->A:T mutations. Thus, UDG is an essential enzyme for maintaining the integrity of genetic information. UDGs have been classified into various families on the basis of their substrate specificity, conserved motifs, and structural similarities. Although these families demonstrate different substrate specificities, often the function of one enzyme can be complemented by the other.
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