DNA is constantly exposed to chemical reactions within its cellular environment, leading to undesired structural changes and compromising the integrity of genetic information.
[5][6] Currently, there are 6 families within the DNA Uracil Glycosylase superfamily, each classified based on their sequence homology, and biochemical and structural similarities.
[6] DNA damage is caused by environmental and endogenous agents, that can create highly mutagenic lesions or compromise genomic stability.
[2] The UDG superfamily typically contains a four-strand β-sheet surrounded by α-helices and undergoes the same or a similar mechanism to create abasic sites.
The general catalytic mechanism involves activating the leaving group, stabilization of the oxocarbenium ion, and positioning of a water molecule.
[10] Structural studies on human uracil DNA glycosylase (PDB 4KSN) suggests a base-flipping mechanism that requires a few key residues.