O6 position of guanine in DNA

The O6 position of guanine is an oxygen atom bonded to the C6 carbon on guanine, one of the four nucleobases in DNA. Alkylation at this position (as in O6-methylguanine) is a major mutagenic lesion that can cause transition mutations (G:C to A:T) if left unrepaired. Such alkylated guanines mispair with thymine during DNA replication. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes alkyl groups from this position, protecting the genome from alkylation-induced mutagenesis and carcinogenesis. In cancer therapy, alkylating agents intentionally produce O6-methylguanine to induce tumor cell death; however, elevated MGMT levels can confer chemoresistance. These lesions also activate DNA damage response pathways that can trigger cell cycle arrest and apoptosis, particularly in the absence of sufficient MGMT-mediated repair.

Other names

O6 atom of guanineO6-guanyl groupO6-guanine lesionO6-methylguanine

Alkylating agents transfer an alkyl (commonly methyl) group onto the O6 atom of guanine, causing mispairing (G:C to A:T transitions) and cytotoxicity. DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes alkyl groups from the O6 position, preventing mutations.