MutY

MutY is a DNA glycosylase that initiates base excision repair by removing mispaired adenine opposite oxidized guanine lesions, most notably 8-oxoguanine (8-oxoG). By excising the adenine from A:8-oxoG mispairs, MutY prevents GC to AT transversions that arise from oxidative DNA damage and helps maintain genomic stability under stress conditions.

In bacteria, MutY is encoded by the mutY gene and is part of the GO (guanine oxidation) repair system along with MutM (Fpg) and MutT. MutY recognizes A mispaired with 8-oxoG or sometimes with guanine and removes the mispaired A, generating an abasic site. An AP endonuclease then cleaves the DNA backbone, after which DNA polymerase fills the gap and ligase seals the strand. MutY proteins belong to the helix-hairpin-helix (HhH)–GPD family of glycosylases and typically bind DNA via a [4Fe-4S] cluster, which is implicated in DNA binding and damage sensing.

In humans and other eukaryotes, the MutY homolog is called MUTYH. It performs a similar base excision repair role, removing adenine opposite 8-oxoG to prevent mutagenesis. Germline mutations in MUTYH cause MUTYH-associated polyposis (MAP), a hereditary colorectal cancer syndrome characterized by multiple polyps and elevated cancer risk. The MUTYH protein functions within a network of base excision repair factors and interacts with other DNA repair pathways to complement oxidative lesion repair.