MGMT

Cancer chemotherapeutic alkylating agents (e.g. BCNU,) act by inducing formation of lethal cross-links at the O6-alkylguanine position in DNA. MGMT transfers alkyl adducts from the O6-position of guanine in DNA (prior to cross-link formation) to a cysteine residue in its own sequence, thereby restoring DNA to its intact state. This transfer inactivates the MGMT enzyme and is irreversible; hence the level of MGMT in a cell is directly proportional to the level of DNA-damage it can tolerate. In normal tissues, MGMT acts as a suppressor of mutation and carcinogenesis. Tumors with high levels of MGMT are likely to be drug resistant.