Protein Clue Could Help Fight Cancer

ATF2 spurs DNA repair, potentially stopping malignant mutations

THURSDAY, May 26, 2005 (HealthDay News) -- In a finding that could have important implications for cancer research, scientists report that the protein ATF2 -- already recognized for its role in gene regulation -- also helps initiate cellular DNA repair.

DNA repair prevents the formation of genetic mutations, including those that cause cancer, and this study is the first to identify ATF2 as playing a role in that process.

"This is the first time we've seen a protein which has been implicated in gene regulation possess an independent function -- in DNA repair -- while both functions are uncoupled from one another," Ze'ev Ronai, director of the signal transduction program at the Burnham Institute, in La Jolla, Calif., said in prepared statement.

Reporting in the May 27 issue of Molecular Cell, the researchers found that ATF2 is activated by a protein kinase called ATM, which in turn stimulates DNA repair. This regulation of ATF2 by ATM is central to a cell's ability to initiate DNA repair, they explained.

"A likely way in which ATF2 works is to halt the cell's cycle to allow repair of damaged DNA before such damage becomes permanent," Ronai said.

The researchers are now exploring how molecules like ATF2 are able to balance their dual roles of gene regulation and DNA repair.

"High doses of radiation, as well as changes that take place in cancer and pathologic situations, can activate both functions of ATF2, which is expected to disturb the otherwise conserved balance between its role in gene regulation and the DNA damage response. We need to find out which of the two functions is more dominant under these circumstances in order to devise ways to regain the upper balance," Ronai said.

More information

The U.S. National Cancer Institute has more about cancer.

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