Charlotte DNA repair research may influence cancer clinical trials

Shan Yan, professor of biological sciences, and his research team recently broke new ground in the functional understanding of the protein APE1 that jumpstarts human DNA damage repair. 

The findings could prove vital to future clinical trials, enabling scientists to possibly test whether therapeutic targeting of naturally occurring but overactive APE1 could improve cancer survival rates.

The work has already been heralded as a “breakthrough study.” And, the paper, published in  Nature Communications, represents the very latest findings from Yan and his NIH-funded lab, which has gained prestigious funding, awards and international recognition over the last decade. 

Central to Yan’s ongoing research is the study of DNA single-strand break repair and signaling pathways. By contrast, much of today’s approach to fighting cancer stems from past research on DNA double-strand break — a lethal type of DNA lesion, long-targeted in cancer therapies.

Pioneering inquiries, however, show that SSBs can foreshadow the development of more lethal DNA damage. Yet, due to lagging research, little was previously known about APE1’s function — what Yan now calls the “molecular switch” that effectively turns on a cell’s attempt to repair SSB damage.

Yan, who also is associate chair for research in the Department of Biological Sciences, said researchers previously “lacked the technical advancement — this complicated design — to study this question.” 

So, as Yan has become known for, he made a path where there was none. 

An earlier breakthrough development of his — a novel highly purified plasmid DNA structure — became the foundation to unlock the latest discovery: how APE1 directly activates ATM signaling to start the repair of single-strand breaks.

In demystifying APE1, Yan said, “These findings will impact the field for years to come.”

Read more about cancer research at UNC Charlotte and recent APE1 findings on the College of Science website at https://science.charlotte.edu/2024/09/16/new-dna-repair-research-may-influence-cancer-clinical-trials/.

Photo: Shan Yan, Haichao Zhao and Jia Li in their research lab.