DNA alkylation by methylation at O6 and N7 positions of guanine bases

DNA alkylation by methylation at O6 and N7 positions of guanine bases is a form of DNA damage primarily induced by the chemotherapeutic agent temozolomide (TMZ). The active metabolite, MTIC, transfers methyl groups to guanine bases, leading to DNA damage, cell cycle arrest, and apoptosis. The most cytotoxic lesion is O6-methylguanine, while N7-methylation is more frequent but less cytotoxic. Resistance to TMZ is often mediated by MGMT, which repairs O6-methylguanine lesions. MGMT expression levels and activity are important determinants of TMZ efficacy.

Other names

Temozolomide-induced DNA alkylationO6-methylguanine formationN7-methylguanine formationDNA Methylation by MTICTMZ-induced DNA damage

Temozolomide is a prodrug that converts to MTIC. MTIC methylates DNA at the O6 and N7 positions of guanine. O6-methylguanine mispairs with thymine leading to futile mismatch repair, double-strand breaks and apoptosis. N7-methylation can cause depurination and strand breaks.