Understanding and manipulating O-6-methylguanine-DNA methyltransferase expression

O-6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that transfers methyl and alkyl lesions from the O-6 position of guanine to a cysteine in its structure. The ability of MGMT to also remove precytotoxic O-6-alkylguanine lesions induced by chemotherapeutic chloroethylnitrosoureas has made down regulation of MGMT expression the key component in strategies designed to sensitize tumors to the cytotoxic potential of chloroethylnitrosoureas. The study of how to regulate MGMT expression at the gene, mRNA, and protein levels has contributed not only to the development of effective inhibitors of MGMT action, but also, in a broader sense, to a better understanding of gene regulation and protein structure/function. (C) 1997 Elsevier Science Inc.