UAMS Receives $3M to Study DNA Structures in Cancer

Key Takeaways:

• UAMS researcher Kevin Raney receives a $2.9 million NIH grant to study DNA quadruplexes and their potential in cancer treatment.
• Quadruplexes may act like natural drugs by binding to proteins like PARP1, a key target in breast cancer therapies.
• The research also explores helicases, proteins essential for DNA repair, as potential therapeutic targets.
• Findings could lead to new ways of controlling cell behavior and developing targeted treatments.

Exploring the Role of Quadruplexes in Disease

USA: The University of Arkansas for Medical Sciences (UAMS) has been awarded a five-year, $2.99 million grant from the National Institutes of Health (NIH) to investigate unusual DNA structures known as quadruplexes. These structures, which form with snippets of damaged genomic DNA, have attracted significant attention in the scientific community due to their potential roles in disease processes.

According to Kevin Raney, Ph.D., professor and chair of the UAMS College of Medicine Department of Biochemistry and Molecular Biology, quadruplexes may offer unique opportunities for targeted therapies. “I think that taking advantage of the quadruplexes’ ability to enter cancer cells more easily than normal cells is an area that’s ripe for pursuing,” Raney said.

Quadruplexes are not merely cellular waste but appear to play significant biological roles. For instance, they can bind tightly to PARP1, a protein involved in repairing damaged genomic DNA and a major target in breast cancer treatment. Existing therapies targeting PARP1 have shown promise, but researchers are actively seeking molecules that can inhibit PARP1 more effectively.

“As it turns out, quadruplex snippets of DNA bind really tightly to PARP1 and inhibit its ability to bind to genomic DNA where it’s normally found,” Raney explained. This suggests that these DNA structures could potentially serve as therapeutic agents rather than signaling molecules.

Insights into Helicases and Their Therapeutic Potential

In addition to studying quadruplexes, the NIH grant supports Raney’s research on helicases, tiny cell motors that help open DNA for reading, copying, or repair. These proteins are essential for maintaining cellular function and are present in both human cells and pathogens like viruses and bacteria.

One unexpected discovery emerged from an experiment Raney described as a “fishing expedition.” His team used magnetic beads coated with quadruplex DNA to capture proteins that bind to these structures. “We were surprised to find that the beads mostly caught helicases,” Raney noted. This finding was facilitated by the IDeA National Resource for Quantitative Proteomics based at UAMS.

The link between helicases and quadruplexes opens new avenues for understanding how cells regulate their behavior. “This work could help us understand how cells protect themselves and, someday, let us use these natural processes to create better treatments,” Raney added.

Implications for Future Treatments

The research conducted under this NIH grant could have far-reaching implications for the development of targeted therapies. By gaining a deeper understanding of how quadruplexes interact with proteins like PARP1 and how helicases contribute to DNA repair, scientists may identify novel ways to control cellular processes.

Raney emphasized the importance of exploring these interactions: “There’s a lot to learn, but we think that there are dozens of interactions between quadruplexes and a variety of drug targets that are out there.”

As the state’s only health sciences university, UAMS plays a critical role in advancing medical research and improving patient care. With its extensive network of institutes and clinical enterprises, the institution is well-positioned to translate scientific discoveries into practical applications.

Conclusion

The NIH grant awarded to UAMS underscores the growing interest in unconventional DNA structures and their therapeutic potential. By investigating quadruplexes and helicases, researchers aim to uncover mechanisms that could lead to more effective treatments for diseases like cancer. While much remains to be discovered, this research represents a meaningful step forward in leveraging natural biological processes to address complex health challenges.