Division Head and Professor of Pharmacology & Toxicology and Doluisio Regents Professor Karen Vasquez, Ph.D. recently published an article in Nature Communications. The study, titled “Obesity increases genomic instability at DNA repeat-mediated endogenous mutation hotspots,” represents the first demonstration that obesity increases genetic instability at alternative DNA structures (in this case H-DNA), which are hotspots for mutations in human cancers.
“We think that this occurs via increased oxidation in the obese state and we know that H-DNA is more susceptible to oxidative DNA damage than the canonical B-DNA duplex (because of its single-stranded junctions, etc.),” says Vasquez, “and we also found that DNA double-strand break repair is less efficient in obese mice than in normal weight mice.” The novel and impactful study took several years to complete.
Authors of the study include former Division of Pharmacology and Toxicology graduate student Pallavi Kompella, Ph.D., Research Assistant Professor Guliang Wang, M.D., Ph.D. and Professor John DiGiovanni, Ph.D., along with Russell E. Durrett, Yanhao Lai, Celeste Marin, Yuan Liu and Samy L. Habib.
The Vasquez Lab's research efforts are focused in three general areas within an overall theme of genome instability, DNA damage and mechanisms of repair. A unique feature of our approach is an emphasis on the role of DNA structure, including non-canonical structures such as triplex DNA, as recognition sites for repair machinery, sources of genomic instability, and as a basis for technology to target DNA damage to specific genomic sites.