FSU researchers uncover new mechanism behind DNA repair

A man in a light blue polo shirt and a man in a navy blue polo shirt pose in a lab with their arms crossed. — FSU College of Medicine’s Daniel Betancourt (left) and Zucai Suo (right) worked with a research team to publish findings that offer new insights into DNA repair and its role in cancer prevention and growth. (Bill Lax/FSU Photography)

Roughly 20 million people receive a cancer diagnosis each year, and an estimated 1-in-5 people will receive a cancer diagnosis in their lifetime. Cancer cells arise from damage to the cell’s instruction manual: DNA.

Researchers in the Department of Biomedical Sciences at Florida State University’s College of Medicine are changing the way scientists think about DNA repair, a process that plays a key role in both cancer prevention and helping some cancers grow.

Our cells contain natural repair machinery that, under normal conditions, cuts out the damaged DNA and fills in the blanks, preventing healthy cells from becoming cancerous. When DNA damage is not repaired, mutations can accumulate in cells and begin growing rapidly. Many cancer cells rely on the same repair machinery but function imperfectly. This can lead to persistent DNA damage and additional mutations accumulating.

For decades, scientists believed polymerase beta (Polβ), one of the key enzymes in the repair process, would form multiple temporary bonds with DNA. The prevailing theory held that Polβ would bind to a DNA strand, detach and then bind again to fill in the missing sequence. New findings suggest the process works differently.

A research team, led by FSU Eminent Professor and Dorian and John Blackmon Chair in Biomedical Science Zucai Suo discovered that Polβ forms a chemical bond with DNA, and proceeds with cutting and repairing the damaged DNA while covalently bonded, or crosslinked, to the strand. By remaining attached during this critical stage of repair, the enzyme is less likely to disengage before the repair process is complete.

Betancourt (left) served as lead author on the team’s publication and Suo (right) led the team’s work. (Bill Lax/FSU Photography)

The research team in FSU’s Department of Biomedical Sciences published their findings uncovering how polymerase beta (Polβ) acts during DNA repair. (Bill Lax/FSU Photography)

“We found that crosslinked Polβ actually enhances the flux — so, basically, enhances its likelihood to move forward and complete the reaction,” said Daniel Betancourt, a doctoral candidate and the lead author on the team’s publication in Nucleic Acids Research. “And so that changes a lot. Polβ has only really been studied when the DNA is not covalently linked to the enzyme.”

Using these findings together with X-ray crystallography snapshots, the Suo lab established a kinetic model that outlines the different step-by-step process for DNA repair while chemically attached to the strand. The model revealed that important repair activities occur while the enzyme remains covalently bound to DNA, a state that had received relatively little attention in previous studies. In this case, Polβ doesn’t detach, or dissociate, after the initial bond is formed. Its work is done while bound to the DNA.

This work, published in June 2026, provides a broader view of DNA damage and repair and lays the foundation for future research to explore how this process occurs naturally and how different forms of DNA damage might influence the repair process.

With these findings in mind, the Suo lab hopes to determine how the initial crosslinking reaction between Polβ and DNA occurs and how that bond sets the stage for successful DNA repair. Their work also establishes a foundation for future studies of at least five other human DNA polymerases involved in DNA repair and damage bypass.