DNAGlykosylase

DNAGlykosylase refers to the class of DNA glycosylases, enzymes that initiate base excision repair by recognizing and removing damaged or inappropriate bases from DNA. They cleave the N-glycosidic bond between the damaged base and the deoxyribose, producing an abasic site that is subsequently processed by AP endonucleases and other BER factors to restore the correct sequence.

Most glycosylases operate by flipping the target base out of the DNA helix into an active site pocket and using catalytic residues to cleave the glycosidic bond. Enzymes in this family can be monofunctional, removing the base but leaving the sugar backbone intact for downstream processing, or bifunctional, which also cleave the backbone at the resulting abasic site via lyase activity. This bifunctionality accelerates repair by combining base removal with strand nicking.

Substrate specificity among DNAGlykosylases varies widely. Uracil-DNA glycosylases remove uracil from single- or double-stranded DNA, while OGG1 targets 8-oxoguanine. The NEIL and NTHL1 families recognize a range of oxidized bases, including pyrimidines, and MUTYH excises adenine mispaired with 8-oxoguanine. TDG removes thymine from G:T mismatches and also processes other substrates. SMUG1 is a more broadly acting glycosylase. In bacteria, Fpg/MutM and Nei proteins perform related functions.

Biological significance is high: proper function of DNAGlykosylases preserves genome integrity, and defects or polymorphisms in these enzymes have been linked to cancer predisposition and aging. They operate within the broader base excision repair pathway, collaborating with endonucleases, polymerases, and ligases to complete repair.