In a new study, lead author Sreerupa Ray, assistant professor of biology at Linfield College, demonstrated how a key enzyme works in repairing damaged DNA.
Ray and her co-authors showed that the enzyme DNA polymerase beta (Pol β) plays a role in DNA double strand repair. The study was published Nov. 17 by Nucleic Acids Research.
DNA is prone to damage by sunlight, chemicals and radiation. One of the most lethal types of damage to DNA is double strand breaks—if left unrepaired, those breaks lead to cell death, genomic instability and cancer formation. In the past, researchers only knew of two ways to repair double strand breaks, but a new way to repair these breaks has been discovered in the past two decades: alternative non-homologous end-joining (aNHEJ).
aNHEJ joins broken DNA ends, but it is error prone, often resulting in the loss or unwanted gain of DNA sequences. aNHEJ requires several processing enzymes. Ray’s research showed for the first time that the enzyme known as DNA polymerase beta (Pol β) plays a role in aNHEJ, and how it works.
“This research impacts the fundamental understanding of the aNHEJ process and has the potential to lead to the design of targeted cancer therapeutics,” Ray said.
“Mutations in DNA repair genes have a significant effect on cancer therapy and outcome,” Ray continued. “Several databases have catalogued DNA repair gene mutations that are found in the tumors of individuals with cancer. However, the biological functions of these mutations and its effect in response to therapy is not known.”
Ray plans to continue research on DNA repair genes, focusing on how cancer-associated variants of DNA repair genes lead to genomic instability. The work will help clarify how the DNA repair mutations impact the formation of tumors and therapy.
Additional authors are Gregory Breuer, Michelle DeVeaux, Daniel Zelterman, Ranjit Bindra and principal investigator Joann B. Sweasy.
