O-6-Methylguanine DNA Methyltransferase (MGMT)

O(6)-alkylguanine is the major mutagenic and carcinogenic lesion in DNA induced by simple alkylating mutagens because of its preference for pairing with thymine during DNA replication. This adduct in DNA is removed by a ubiquitous and unique repair protein, O(6)-methylguanine-DNA methyltransferase (EC 2.1.1.63).

Methylated-DNA--protein-cysteine methyltransferase, unlike true enzymes, accepts the alkyl group from the lesion in a stoichiometric second-order reaction. The methyl-acceptor residue is cysteine. Tano et al. (1990) cloned the cDNA of the human MGMT gene in an expression vector on the basis of its rescue of a methyltransferase-deficient E. coli host.