Locating Noncanonical DNA Structures (i.e., Z-DNA, Triplex DNA, G4-quadruplex DNA, and i-Motif DNA) in Metabolic Genes (i.e., FH, SDHD, PKM2, and IDH1): The Warburg Effect, Cancer and Genomic Instability

Student Presenter(s): Juliana D’Amico, Anamika Rao, Prutha Patel, and Lina Elkoulily
Faculty Mentor: Claude Gagna
School/College: Arts and Sciences, Old Westbury

The majority of organismal DNA is canonical right-handed double-stranded (ds-) B-DNA. However, DNA is a dynamic entity that can assume different structures, such as Z-DNA, triplex DNA, G4-quadruplex DNA, i-motif quadruplex DNA, cruciform DNA, hairpin DNA, anti-parallel DNA, and curved DNA. Using three different DNA prediction softwares [i.e., DeepZ (Z-DNA), Triplex Aligner (Triplex DNA), G4Boost (G4-quadruplex DNA), and G4-iM Grinder (i-motif quadruplex DNA)], we examined four metabolic genes (i.e., FH, SDHD, IDH1, PKM2) involved in the Warburg effect and cancer. Left-handed Z-DNA is an alternative ds-DNA molecule. Triplex DNA, G4-quadruplex DNA and i-motif DNA are all multistranded molecules. These unusual DNAs play roles in maintaining normal gene expression and developing pathological conditions. Warburg discovered that the majority of glucose consumed by tumors is fermented to lactate rather than oxidized in pathways that require respiration. His ideas were forgotten for years, until recently, when cancer researchers reexplored his hypothesis that cancer is a metabolic disease rather than a genetic pathology of nuclear DNA. No one has ever examined any metabolic genes for noncanonical DNAs. It’s important to locate noncanonical DNAs because these exotic DNA structures play a role in gene instability, which can result in cancer. Knowing the potential segments in genes that contain unusual DNA structures will allow for the development of anti-cancer precision therapies.