Uracil-DNA glycosylase (EC 3.2.2.-) (UNG) [1] 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 misincorportation of dUMP residues by DNA
polymerase or deamination of cytosine.
The sequence of uracil-DNA glycosylase is extremely well conserved [2] in
bacteria and eukaryotes as well as in herpes viruses. More distantly related
uracil-DNA glycosylases are also found in poxviruses [3].
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 [4]. The N-terminal 77 amino acids of UNG1 seem to be required for
mitochondrial localization [4], but the presence of a mitochondrial transit
peptide has not been directly demonstrated.
As a signature for this type of enzyme, we selected the most N-terminal
conserved region. This region contains an aspartic acid residue which has been
proposed, based on X-ray structures [5,6] to act as a general base in the
catalytic mechanism.
Note:
In humans, two additional sequences of UNG have been reported [7,8].
These isozymes are not evolutionary related to other known UNG. One of them
is a glyceraldehyde 3-phosphate dehydrogenase [8] and the other related to
cyclins [9]. Data available on three proteins proposed to be human uracil-DNA
glycosylases is discussed in [10].
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