MSU Researchers Illuminate DNA Repair Dynamics with Breakthrough Imaging Techniques

East Lansing, MI — A groundbreaking study from Dr. Jens Schmidt’s lab at the Institute for Quantitative Health Science & Engineering (IQ) at Michigan State University has shed new light on the molecular mechanics of DNA repair. Published in Nature Communications, this research unveils the first-ever real-time, single-molecule insights into the repair process of DNA double-strand breaks (DSBs) in living cells – a pivotal advancement for understanding genomic stability and potential cancer therapies.

DNA DSBs represent one of the most hazardous forms of genetic damage. When both strands of the DNA helix are severed, cells rely heavily on the non-homologous end joining (NHEJ) repair pathway to maintain genomic integrity. Without accurate and swift repair, these breaks can lead to mutations or chromosomal rearrangements, which are precursors to cancer development.

The team at IQ, led by graduate student Mariia Mikhova and Dr. Schmidt, has developed a state-of-the-art live-cell imaging approach to visualize and measure how NHEJ factors operate, providing clarity into this crucial biological process.

Using cutting-edge single-molecule imaging, the researchers tagged key NHEJ proteins with fluorescent markers, enabling real-time tracking of their recruitment to DNA damage sites. This allowed the team to quantify the capacity of the NHEJ pathway in living cells for the first time. Their findings revealed that human cells can repair up to 1,100 DNA breaks per minute via NHEJ, highlighting the remarkable efficiency of this repair mechanism.

One key finding was how DNA repair happens in distinct steps. First, specialized proteins recognize and stabilize the broken DNA ends. Then, they work together to build a repair complex that can reconnect the strands. The team also identified specific actions within this process that are carefully controlled, ensuring the repair moves smoothly from recognizing the damage to completing the repair.

Beyond its significance in basic biology, this research has profound implications for cancer therapy. Many cancer treatments, such as radiation and certain chemotherapies, work by inducing DNA damage in tumor cells. Understanding the intricate dynamics of DNA repair pathways can guide the development of targeted therapies that exploit vulnerabilities in cancer cells’ repair mechanisms.

“Tumors often have deficiencies in specific DNA repair pathways, which drive the mutations that turn normal cells into cancerous ones,” Dr. Schmidt explained. “Our findings provide a framework for understanding these deficiencies and could inform strategies to design therapies that selectively kill cancer cells.”

This study represents the culmination of a multi-disciplinary collaboration with MSU’s Department of Microbiology, Genetics, and Immunology. Dr. Kathy Meek, an expert in NHEJ