O^6^-methylguanine-DNA methyltransferase (MGMT)

O^6^-methylguanine-DNA methyltransferase (MGMT) is a crucial DNA repair enzyme that protects cells from mutagenic and cytotoxic effects of alkylating agents by removing alkyl groups from the O^6 position of guanine. This direct reversal mechanism prevents mismatches during replication and transcription. The enzyme acts through a “suicide” reaction—each molecule can only catalyze one reaction before being inactivated. Loss or silencing of MGMT increases susceptibility to carcinogenesis after exposure to environmental or therapeutic alkylating agents. In cancer therapy, especially for glioblastoma, the level of MGMT expression or promoter methylation serves as an important biomarker for predicting tumor sensitivity or resistance to certain chemotherapies such as temozolomide[1][2][4].\n\n**Note:** The submitted target name "DNA guanine O6-methyltransferase substrate site" is not itself a canonical molecular target but refers instead to the specific lesion repaired by this enzyme; thus it is considered incorrect as a standalone therapeutic target designation[1]. The correct molecular target is "O^6^-methylguanine-DNA methyltransferase" (MGMT).

Other names

Methylated-DNA–protein-cysteine methyltransferaseO^6^-alkylguanine DNA alkyltransferaseAGTO^6^-methylguanine-DNA methyltransferase substrate site (incorrect as a target name)

Direct removal of alkyl groups from the O^6 position of guanine in DNA via stoichiometric transfer to a cysteine residue on MGMT (“suicide” mechanism)[1][2][5]