Uracil-DNA glycosylase (UDG, UNG) []is a DNA repair enzyme that excises uracil residues from DNA by cleaving the N-glycosylic bond. Uracil in DNA can arise as a result of mis-incorporation of dUMP residues by DNA polymerase or deamination of cytosine. UDGs were classified into 4 families [, ].Family 1 enzymes are active against uracil in both ssDNA and dsDNA, and recognise uracil explicitly in an extrahelical conformation via a combination of protein and bound-water interactions []. Family 1 enzymes are present in Eubacteria, Eukarya and in some eukaryotic viruses. The sequence of uracil-DNA glycosylases is extremely well conserved []in bacteria and eukaryotes as well as in herpes viruses []. More distantly related uracil-DNA glycosylases are also found in poxviruses []. In eukaryotic cells, UNG activity is found in both the nucleus and the mitochondria. Human nuclear UNG2 and mitochondrial UNG1are both encoded by the UNG gene [, ]. The N-terminal 77 amino acids of UNG1 seem to be required for mitochondrial localisation []. The catalytic C-terminal domains of UNGs are highly conserved at both the sequence and structure level while the N-terminal domains are diverse and are thought to be involved in subcellular localisation and protein-protein interactions [].
Uracil-DNA glycosylase (UNG) []is a DNA repair enzyme that excises uracil residues from DNA by cleaving the N-glycosylic bond. Uracil in DNA can arise as a result of mis-incorporation of dUMP residues by DNA polymerase or deamination of cytosine.The sequence of uracil-DNA glycosylase is extremely well conserved []in bacteria and eukaryotes as well as in herpes viruses. More distantly related uracil-DNA glycosylases are also found in poxviruses []. In eukaryotic cells, UNG activity is found in both the nucleus and the mitochondria. Human UNG1 protein is transported to both the mitochondria and the nucleus []. The N-terminal 77 amino acids of UNG1 seem to be required for mitochondrial localisation [], but the presence of a mitochondrial transitpeptide has not been directly demonstrated. The most N-terminal conserved region contains an aspartic acid residue which has been proposed, based on X-ray structures [, ]to act as a general base in the catalytic mechanism.This signature pattern covers the most N-terminal conserved region, which contains an aspartic acid residue that has been proposed, based on X-ray structures [, ]to act as a general base in the catalytic mechanism.
