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New understanding of DNA repair may pave way to cancer treatments

owth was primarily through its established function in the regulation of proteins important in cell cycle and cell death control. We were therefore most surprised to find an uncoupled function for the same protein," said Ronai.

The finding of ATF2's novel function in DNA repair was serendipitous. As Shoichi Takahashi, a postgraduate researcher, was testing for the changes in ATF2 in human cancers, he "lost the signal" for ATF2. "Later," Dr. Ronai said, "we did experiments that showed the signal was lost because a protein kinase, ATM, modified ATF2 enough to interfere with detection of the ATF2 signal. Soon, work performed by Anindita Bhoumik confirmed that ATF2 is regulated by ATM and that this regulation is central to the cell's ability to initiate DNA repair processes following ionizing irradiation or other exposures that cause breaks in DNA. 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 and his colleagues are now determining how molecules like ATF2 can balance their dual roles. "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 proper balance," he said.

The Ronai lab's work on ATF2 was started at Mount Sinai School of Medicine in New York City, from which Dr Ronai and his colleagues recently relocated to the Burnham Institute. This study was carried out in collaboration with Wolfgang Breitweiser and Nic Jones of the Paterson Institute for Cancer Research, Manchester, England, and Yosef Shiloh, of Tel Aviv University, Israel. The study was supported by a grant from the National Institutes of Health.


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Source:Burnham Institute


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