O6-alkylguanine lesion in DNA

Alkylation of guanine bases in DNA is a chemical modification, typically at the O6 position of guanine, resulting from exposure to endogenous or exogenous alkylating agents. This lesion can cause mutagenic mispairing (G:C to A:T mutations) during DNA replication and contributes to carcinogenesis and cytotoxicity. Cells possess direct DNA repair systems—primarily O6-methylguanine-DNA methyltransferase (MGMT)—that remove alkyl groups, thereby reversing the DNA damage. Many anticancer alkylating agents exert their cytotoxic effects by inducing guanine alkylation, while cancer resistance can emerge via increased MGMT activity which counteracts this lesion[1][2][4][5][7][9].

Other names

alkylated guanineO6-alkylguanine lesionO6-methylguanineguanine alkylationDNA alkylation adducts

Alkylating agents *cause* DNA alkylation at guanine, resulting in cytotoxic/mutagenic lesions[2][4][5][9]\nDNA repair agents *remove* alkyl groups, reversing alkylation[1][2][3][4][7]