MGMT

Cancer chemotherapeutic alkylating agents (e.g. BCNU,) act by inducing the 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 toleration. In normal tissues, MGMT acts as a suppressor of mutation and carcinogenesis. Tumors with high levels of MGMT are likely to be drug resistant.