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Why damaged DNA gets a case of the bends

Study reveals how body's repair machinery recognizes altered DNA

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August 22, 2004 Share This!

PHILADELPHIA — Our knees may become stiff when injured, but banged up DNA becomes flexible, suggests the most detailed computer model of damaged DNA to date. Further, this flexibility explains how the body's enzymes recognize and fix damaged DNA, Pacific Northwest National Laboratory's Maciej Haranczyk reported today at the American Chemical Society national meeting.

"There's a lot of discussion in the literature about how damaged DNA is recognized by the repair enzymes," said Haranczyk, a staff scientist at the Department of Energy laboratory in Richland, Wash. "The current picture is that some enzymes bend damaged DNA in order to repair altered fragments. But no one knew why damaged DNA was more susceptible to bending."

Haranczyk and colleagues' simulation offers an explanation. First, they programmed a chemical change to an intact DNA fragment. As with real DNA, the simulated molecule's backbone became distorted and its base pairs displaced. The structural change corresponded with a change in the molecule's shape, in its energy and how electric charges are distributed throughout the molecule.

"All these features are significant in enzymatic recognition of the damaged site," Haranczyk said. "In our model, damage triggers a reorganization of the sugar-phosphate in the DNA's backbone such that the DNA becomes thinner. In damaged DNA, negatively charged phosphate groups migrate along the axis of the DNA, and that allows the molecule to bend easily. We believe it is this difference in the damaged and intact DNA that the enzymes recognize."

Haranczyk said this was the first quantum chemistry simulation to survey such a large biological system-in this case, a DNA fragment made up of 350 atoms. "With a system so big, one can't do this kind of work without a supercomputer. Fortunately, we had access to one of the world's 10 most powerful computers," housed at the W.R. Wiley Environmental Molecular Sciences Laboratory on the PNNL campus.

Tags: Energy, Fundamental Science, Computational Science, Chemistry, Supercomputer

PNNL LogoInterdisciplinary teams at Pacific Northwest National Laboratory address many of America's most pressing issues in energy, the environment and national security through advances in basic and applied science. Founded in 1965, PNNL employs 4,400 staff and has an annual budget of nearly $1 billion. It is managed by Battelle for the U.S. Department of Energy's Office of Science. As the single largest supporter of basic research in the physical sciences in the United States, the Office of Science is working to address some of the most pressing challenges of our time. For more information on PNNL, visit the PNNL News Center, or follow PNNL on Facebook, Google+, Instagram, LinkedIn and Twitter.

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