Clemson biochemist receives grants to study DNA repair pathways

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A Clemson biochemist has received grants totaling $787,000 to study how cells repair damaged DNA, which can cause cancer and genetic illnesses. The U.S. Department of Defense (DoD) and the National Institutes of Health (NIH) awarded Weiguo Cao three-year funding to investigate two DNA repair pathways.

"We hope these studies will not only help us understand the basic mechanisms of DNA repair but also help us understand how DNA repair contributes to cancer prevention," said Cao, associate professor in the genetics and biochemistry department.

The integrity of the DNA sequence is important for proper cell function. Mutations to its chemical structure are most commonly corrected by DNA repair, a biochemical tool kit that fixes breaks and mistakes in the genetic code. DNA-repair proteins can search through pieces of DNA to find subtle mistakes in the code and repair them. It is necessary because genes are continually assaulted by "troublemakers" inside cells and from the environment.

Unrepaired DNA can lead to mutations, which may accumulate and lead to cancer and other illnesses. Some of the drugs used in cancer treatments work by intentionally damaging DNA. Their success can be influenced by DNA repair activities. A clearer understanding of DNA repair may offer to improve cancer therapy.

"The link between DNA repair and cancer is well known in some instances," Cao said. "For example, some people are susceptible to skin cancer due to defect in DNA repair.

"My lab studies a repair process for another cause of DNA mistakes: deamination. Deamination damages DNA, causing part of the genetic code to be copied wrong that results in mismatched pairings of biochemicals that contain the instructions for proper cell function," he said. "We want to know how DNA repair enzymes find the damage and remove it. The research can help understand how defects in repair of deaminated DNA cause cancer."

Military personnel and civilians alike are exposed to various cellular stresses: inflammation, infection, genetic code duplication errors, ultraviolet light, air pollution and cancer-causing substances. DNA in a cell may be damaged more than 10,000 times a day. DNA repair functions so well that there is less than a one-in-a-billion chance for a mutation to take hold.

Cao is grateful for funding. "I appreciate the support of the DoD and NIH provided to my lab in this challenging time for research grants," he said.

Papers by Cao's and his collaborators' laboratories that describe the DNA repair research have been published in such international journals as the Journal of Molecular Biology, Nature Structural and Molecular Biology, and the Journal of Biological Chemistry.

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