DNA glycosylases (EC 3.2.2.) are a family of enzymes involved in base excision repair (BER) and catalyze the first step of this process. They recognize and remove the damaged nitrogenous base while leaving the sugar-phosphate backbone intact, creating an apurinic/apyrimidinic site, commonly referred to as an AP site. This is accomplished by flipping the damaged base out of the double helix followed by cleavage of the N-glycosidic bond. There are two main classes of glycosylases: (i) monofunctional and (ii) bifunctional.
Bifunctional glycosylases also possess AP lyase activity and can therefore convert a base lesion into a single-strand break without the need for an AP endonuclease. β-elimination of an AP site by a glycosylase-lyase yields a 3' α,β-unsaturated aldehyde adjacent to a 5' phosphate, which differs from the AP endonuclease cleavage product.
Some glycosylase-lyases can further perform δ-elimination, which converts the 3' aldehyde to a 3' phosphate.
Based on structural similarity, glycosylases are grouped into four superfamilies. The UDG and AAG families contain small, compact glycosylases (monofunctional), whereas the MutM/Fpg and HhH-GPD families comprise larger enzymes with multiple domains (bifunctional).