del Mundo, Imee M. A.Zewail-Foote, MahaKerwin, Sean M.Vasquez, Karen M.2020-04-032020-04-032017-02del Mundo, I. M. A., Zewail-Foote, M., Kerwin, S. M., & Vasquez, K. M. (2017). Alternative DNA structure formation in the mutagenic human c-MYC promoter. Nucleic Acids Research, 45(8), pp. 4929–4943.0305-1048https://hdl.handle.net/10877/9575Mutation 'hotspot' regions in the genome are susceptible to genetic instability, implicating them in diseases. These hotspots are not random and often co-localize with DNA sequences potentially capable of adopting alternative DNA structures (non-B DNA, e.g. H-DNA and G4-DNA), which have been identified as endogenous sources of genomic instability. There are regions that contain overlapping sequences that may form more than one non-B DNA structure. The extent to which one structure impacts the formation/stability of another, within the sequence, is not fully understood. To address this issue, we investigated the folding preferences of oligonucleotides from a chromosomal breakpoint hotspot in the human c-MYC oncogene containing both potential G4-forming and H-DNA-forming elements. We characterized the structures formed in the presence of G4-DNA-stabilizing K⁺ ions or H-DNA-stabilizing Mg2⁺ ions using multiple techniques. We found that under conditions favorable for H-DNA formation, a stable intramolecular triplex DNA structure predominated; whereas, under K⁺-rich, G4-DNA-forming conditions, a plurality of unfolded and folded species were present. Thus, within a limited region containing sequences with the potential to adopt multiple structures, only one structure predominates under a given condition. The predominance of H-DNA implicates this structure in the instability associated with the human c-MYC oncogene.Text15 pages1 file (.pdf)enDNA structure formationmutation regionsc-MYC oncogeneChemistry and BiochemistryArticle© 2017 The Author(s).https://doi.org/10.1093/nar/gkx100This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.