Uracil-DNA glycosylase, also known as UNG or UDG, catalyzes the hydrolysis of the N-glycosylic bond between the uracil and sugar, leaving an abasic site in uracil-containing single or double-stranded DNA. The enzyme shows no measurable activity on short oligonucleotides (<6 bases), or RNA substrates.
The first uracil DNA-glycosylase was isolated from Escherichia coli. One important function of uracil-DNA glycosylases is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosylic bond and initiating the base-excision repair (BER) pathway. Uracil bases occur from cytosine deamination or misincorporation of dUMP residues. After a mutation occurs, the mutagenic threat of uracil propagates through any subsequentDNA replication steps. Once unzipped, mismatched guanine and uracil pairs are separated, and DNA polymerase inserts complementary bases to form a guanine-cytosine (GC) pair in one daughter strand and an adenine-uracil (AU) pair in the other. Half of all progeny DNA derived from the mutated template inherit a shift from GC to AU at the mutation site. UDG excises uracil in both AU and GU pairs to prevent propagation of the base mismatch to downstream transcription and translation processes. With high efficiency and specificity, this glycosylase repairs more than 10,000 bases damaged daily in the human cell. Human cells express five to six types of DNA glycosylases, all of which share a common mechanism of base eversion and excision as a means of DNA repair.