An important element of DNA repair is the focus of a $208,000 National Institutes of Health grant awarded to a researcher at East Tennessee State University’s James H. Quillen College of Medicine.
Environmental hazards, such as UV irradiation and toxic chemicals, are major contributors to DNA damage. Two crucial pathways – DNA repair and DNA damage checkpoints – help remove the damaged DNA and maintain the integrity of the human genome.
“But if there is some type of malfunction within those pathways, the damaged DNA could replicate, eventually leading to cancer or other diseases,” said study principal investigator Dr. Yue Zou, a professor of Biochemistry and Molecular Biology at ETSU. Dr. Phillip Musich, also a professor of Biochemistry and Molecular Biology, is the co-investigator on this grant.
Zou explains that a protein known as Replication protein A (RPA) plays a critical role in DNA damage checkpoint signaling, as well as the regulation of DNA metabolic processes such as repair, replication and recombination. RPA undergoes a chemical modification process called hyperphosphorylation that alters the functions of the protein and allows the activities of the cellular pathways to be changed.
“Our goal is to understand the mechanisms of RPA hyperphosphorylation,” Zou said. “RPA has some type of involvement in nearly all DNA metabolic pathways, and a better understanding may identify new strategies for cancer treatment.

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