Role of FRAP in DNA Damage Control and Breast Cancer Therapy

摘要

Genomic DNA is the fundamental hereditary material that passes from generation to generation. In cells, the integrity of DNA is vulnerable to environmental hazards such as radiation and certain chemicals, which can result in DNA damage and thus genetic alterations. Such DNA damage may also arise from attack by intracellular, chemically reactive molecules which are byproducts of normal metabolic processes. Unrepaired DNA often leads to conditions that are favorable for development of abnormalities in cells and organisms, or diseases in humans such as cancer. As a result, the cell has evolved an effective way to detect and repair DNA damage before it divides. ATM is a key player in DNA damage responses. Together with a number of other damage control proteins, it detects DNA damage and sends the damage signal to temporarily halt cell division and mobilize cellular enzymes to fix DNA molecules. We show some evidence that mTOR/FRAP, a member of the ATM kinase family, may have a role in DNA damage control by directly interacting with DNA. This observation suggests that rapamycin, a highly specific inhibitor of mTOR/FRAp, may be used to sensitize ionizing radiation therapy of breast cancer.