DNA Repair Methyltransferase II, also known as MGMT (O-6-methylguanine-DNA methyltransferase), is a protein that plays a crucial role in DNA repair mechanisms. It is an enzyme involved in maintaining the integrity of the DNA molecule by removing alkyl groups from the O-6 position of guanine, which can be damaged by various environmental factors, such as radiation and certain chemical agents.
DNA repair is essential for the proper functioning and replication of DNA. This process prevents the accumulation of mutations and ensures the stability of the genetic material. MGMT is specifically responsible for the repair of O-6-alkylguanine lesions, which occur when alkylating agents add an alkyl group to the O-6 position of guanine in DNA. These lesions can lead to DNA damage and cause genetic mutations if left unrepaired.
MGMT works by accepting the alkyl group from the damaged DNA molecule, thereby transferring it to its own active site cysteine residue. This transfer process effectively removes the alkyl group from the DNA, restoring the normal guanine molecule. However, this repair mechanism is unique because MGMT irreversibly modifies itself during the process, leading to its degradation and consequent depletion in the cell.
The importance of MGMT in DNA repair is highlighted by its role in resistance to certain chemotherapeutic agents, such as alkylating drugs. Cancer cells with high levels of MGMT expression tend to be more resistant to these drugs as MGMT can repair the drug-induced DNA damage, rendering the treatment less effective. Conversely, reduced levels or loss of MGMT function in cancer cells can enhance the efficacy of alkylating drugs.
Understanding the role and function of DNA Repair Methyltransferase II is crucial in the development of cancer therapies and
