MutM

MutM, also known as Fpg (formamidopyrimidine-DNA glycosylase), is a DNA repair enzyme that initiates base excision repair of oxidative lesions in bacteria. It is a member of the HhH-GPD family of DNA glycosylases and is widely present in bacteria.

MutM recognizes oxidized purines in double-stranded DNA, with 8-oxoguanine (8-oxoG) and formamidopyrimidine lesions among the preferred substrates. It excises the damaged base by hydrolyzing the N-glycosidic bond, generating an abasic site. In many bacteria, MutM also possesses AP lyase activity, cleaving the DNA backbone at the abasic site via beta-elimination to produce a single-strand break that is subsequently processed by downstream BER enzymes such as AP endonuclease and DNA polymerase.

Biological role: 8-oxoG is a major lesion arising from reactive oxygen species and can mispair with A during replication, yielding G:C to T:A transversions. By removing 8-oxoG, MutM reduces mutagenesis and works in concert with MutY glycosylase, which removes A opposite 8-oxoG to correct mispairs, forming a coordinated repair pathway.

Genetics and evolution: The mutM gene encodes this enzyme in Escherichia coli and many bacteria. The enzyme is widely conserved and has homologs across domains; in eukaryotes, related 8-oxoG glycosylases (such as OGG1) fulfill similar roles in different repair pathways.