Researchers discover DNA repair scheme could help better treat cancer

A team of researchers from Rice University and St. Jude Children's Research Hospital in Memphis, Tennessee have discovered an enzyme called DNA polymerase theta, or Pol theta, that can be used as a promising way to treat cancer.

Their findings were published in the Nucleic Acids Research journal, according to a press release. 

“I love this project,” Chuxuan Li, a Rice University post doctoral researcher, said. “I think there’s so much that can be done specifically for this enzyme, because it’s so unique. I believe more people will be motivated to look into this particular protein.”

Pol theta plays a crucial role in the process of microhomology-mediated end joining (MMEJ), a DNA repair mechanism that is essential for fixing double-strand breaks in DNA. MMEJ is a complementary process to two other repair mechanisms, homologous recombination, and non-homologous end joining, but with lower fidelity, due to Pol theta's propensity for insertion and deletion errors.

This susceptibility to errors, however, also presents an opportunity for cancer therapy. According to the release, MMEJ requires Pol theta to repair a double strand, and the researchers found that by inhibiting Pol theta, they could selectively target cancer cells while leaving normal cells unharmed. The researchers conducted experiments on proteins drawn from the Asian sea bass, but they plan to continue their work on the human version of Pol theta. 

In addition to Li, the study's co-authors include Rice assistant professor of biosciences, Yang Gao, St. Jude's assistant member of the Structural Biology Department, Ji Sun, and postdoctoral researcher, Hanwen Zhu, of St. Jude. The research was supported by several organizations, including the Cancer Prevention and Research Institute of Texas (CPRIT), the American Cancer Society, the National Institutes of Health, and the Welch Foundation, the release noted.

In the release, Gao said clinical trials of Pol theta inhibitors are already underway based on research by other labs, but their study adds important details about the mechanism behind MMEJ repair. The team's work on Pol theta could open up new avenues for cancer therapy and help researchers develop more targeted and effective treatments for the disease.