Adenine DNA glycosylase (MUTYH)

Adenine DNA glycosylase (MUTYH) is an enzyme crucial for base excision repair of oxidative DNA damage. It specifically recognizes and excises adenine bases mispaired with guanine, cytosine, or particularly the oxidized base 8-oxoguanine (8-oxoG), preventing G:C to T:A transversion mutations that can lead to carcinogenesis. MUTYH localizes to both the nucleus and mitochondria, participating in genomic maintenance in both compartments. Mutations in the human MUTYH gene cause MUTYH-associated polyposis (MAP), a hereditary syndrome marked by increased colorectal cancer risk and, in some cases, other cancers. Within the cell, MUTYH interacts with several partners, including PCNA (a DNA replication clamp), the Rad9-Rad1-Hus1 complex (DNA damage response), and APE1 (essential for the next DNA repair step). Experimental evidence also shows MUTYH expression can be altered by certain chemicals, including tamoxifen and ethinylestradiol. As a DNA repair enzyme, inhibitors of MUTYH are mainly experimental and used to study its mechanistic biology, rather than for therapy at this time. Testing for MUTYH mutations is used clinically as a cancer risk biomarker, especially for colorectal cancer syndromes. Biallelic loss-of-function mutations result in increased DNA damage accumulation, driving tumorigenesis and other genomic instability disorders.

Other names

MutY DNA glycosylaseMYHhMYHmutY homologmutY-like proteinA/G-specific adenine DNA glycosylase

Glycosylase inhibitors (DNA substrate analogs, experimental) and modulation of expression for cancer prevention or therapy.