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NCI-supported scientists at St. Jude's Children's Research Hospital in Memphis have discovered an early, critical process that helps cells respond to DNA damage. The finding opens exciting opportunities for cancer prevention, for enhancing radiation therapy, and for protecting healthy cells during cancer treatment. It also may lead to an assay for assessing exposure to toxins and other dangerous agents in the environment.
The process involves modifying an enzyme called ATM, which when activated sets off a cascade of reactions that halt the growth of a damaged cell and enable its repair and survival. The scientists developed an antibody that can specifically identify those ATM molecules that are responding to DNA damage. The antibody showed that damaged DNA signals the ATM to instigate repair within seconds of the damage occurring.
The scientists, led by Michael B. Kastan, M.D., Ph.D., envision several potential ways this new pathway could be manipulated. For example, ATM is central to a cell's response to radiation, so blocking its activity might make a tumor much more vulnerable to radiation therapy. Enhancing the repair process may prevent cancer development or help healthy cells in the body better tolerate exposure to cancer treatments. Kastan's group and several biotech companies are screening compounds to find those that can affect this pathway.
Among the proteins affected by activated ATM are BRCA1 and p53. These proteins play important roles in preventing cancer. When altered, they are responsible for inherited cancers, such as familial breast cancer. The new finding provides new insight into the way cells signal to BRCA1 and p53 following DNA damage.
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