TY - JOUR
AU - Vasquez, Karen M.
AB - AbstractMutation ‘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.
TI - Alternative DNA structure formation in the mutagenic human c-MYC promoter
JF - Nucleic Acids Research
DO - 10.1093/nar/gkx100
DA - 2017-05-05
UR - https://www.deepdyve.com/lp/oxford-university-press/alternative-dna-structure-formation-in-the-mutagenic-human-c-myc-5onvgR30KU
SP - 4929
EP - 4943
VL - 45
IS - 8
DP - DeepDyve
ER -