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Nature's elegant solution to repairing DNA in cancer, other conditions
Date:4/20/2011

DURHAM, N.C. A major discovery about an enzyme's structure has opened a window on understanding DNA repair. Scientists at Duke University Medical Center have determined the structure of a nuclease that will help scientists to understand several DNA repair pathways, a welcome development for cancer research.

DNA repair pathways are very important in the context of cancer biology and aging, but the tools the cell uses to do those repairs are not well understood.

"Until we saw the structure using X-ray crystallography, we didn't understand how it could recognize so many unusual DNA structures," said senior author Lorena Beese, Ph.D., James B. Duke Professor of Biochemistry. "The relative arrangement of the binding sites and of the active site itself for this enzyme is important for recognition during the repair process, and I don't think we could have imagined how it came together."

The study appears in this week's issue of Cell journal.

"We present the first structural information about these nucleases in humans, and that information is important for DNA substrate recognition and enzymatic mechanism," Beese said. "The discovery is important for understanding the mismatch repair pathway, and more generally, it will help us understand other pathways as well."

If mismatch repairs are not completed properly, this deficiency can have profound effects on human health, including genes that mutate spontaneously, forms of colorectal cancer, and the development of an estimated 15-25 percent of sporadic tumors, the authors noted.

"Scientists have been interested in obtaining a detailed picture of where the atoms are in this protein for a long time. We were able to determine the structure, because we put together the right experiments at the right time good protein expression, good purification, and fortunately when we got crystals we had the right team to solve the structure and do the biochemical experiments,"
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Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

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