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Newly discovered cellular process helps cells respond to DNA damage

Scientists at St. Jude Children's Research Hospital have discovered a novel biochemical process that plays a critical role in helping cells in the body respond to DNA damage, such as that caused by exposure to radiation, environmental toxins or free radicals.

The findings could lead to new approaches to prevent cancer, better ways to treat cancer and to the development of sensitive methods determining whether people have been exposed to radiation or environmental toxins, according to the researchers.

A report on this discovery, published in the current issue of the journal Nature, describes this critical early step in a cell's response to DNA damage. This step, a chemical modification of an enzyme called ATM, allows the enzyme to initiate a series of events that ultimately halt the growth of a damaged cell and help the cell survive.

The finding is important because DNA damage caused by radiation and environmental toxins can lead to mutations or cell death, and can also contribute to the development of cancers.

Michael Kastan, M.D., Ph.D., chair of the Department of Hematology-Oncology at St. Jude and Christopher Bakkenist, Ph.D., also of St. Jude co-authored the research.

The St. Jude researchers found that ATM is activated by a signal from damaged DNA only seconds after the damage occurs. The activated ATM, in turn, activates other proteins by attaching a molecule called "phosphate" to them in a process called phosphorylation. This sets off a cascade of biochemical reactions that amplifies the initial ATM response.

Among the proteins phosphorylated by ATM are Brca1 and p53. It was already known that these proteins play important roles in preventing cancer, and that mutated forms of Brca1 and p53 are responsible for inherited cancers, such as familial breast cancer. The new St. Jude findings thus provide new insights into the way cells signal to both Brca1 and p53 following DNA damage.

The scientists are ho
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
29-Jan-2003


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