Alternative DNA Structure Formation in the Mutagenic Human c-MYC Promoter
del Mundo, Imee M. A.
Kerwin, Sean M.
Vasquez, Karen M.
Oxford University Press
Mutation '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.
DNA structure formation, mutation regions, c-MYC oncogene, Chemistry and Biochemistry
del 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.