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.
Monofunctional glycosylases have only glycosylase activity and to cleave the N-glycosidic bond, use an activated water molecule to attack carbon 1 of the substrate.
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).