6-O-Methylguanine

6-O-Methylguanine is a derivative of the nucleobase guanine in which a methyl group is attached to the oxygen atom. It base-pairs to thymine rather than cytidine, causing a G:C to A:T transition in DNA.

Formation

6-O-methylguanine is formed in DNA by alkylation of the oxygen atom of guanine, most often by N-nitroso compounds (NOC) and sometimes due to methylation by other compounds such as endogenous S-adenosyl methionine. NOC are alkylating agents formed by the reaction of nitrite or other nitrogen oxides with secondary amines and N-alkylamides, yielding N-alkylnitrosamines and N-alkylnitrosamides.

NOC are found in some foods (bacon, sausages, cheese) and tobacco smoke, and are formed in the gastrointestinal tract, especially after consumption of red meat. In addition, endogenous nitric oxide levels were found to be enhanced under chronic inflammatory conditions, and this could favor NOC formation in the large intestine.

Repair and carcinogenicity

Repair of 6-O-methylguanine in DNA is primarily carried out by O-6-methylguanine-DNA methyltransferase (MGMT). Epigenetic reductions in MGMT expression are one of the most frequent DNA repair defects, associated with carcinogenesis. (Also see MGMT expression in cancer.)