Alternative DNA structure formation in the mutagenic human c-MYC promoter.
Nucleic Acids Res
; 45(8): 4929-4943, 2017 05 05.
Article
in En
| MEDLINE
| ID: mdl-28334873
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligonucleotides
/
DNA
/
Proto-Oncogene Proteins c-myc
/
Nucleic Acid Conformation
Limits:
Humans
Language:
En
Journal:
Nucleic Acids Res
Year:
2017
Document type:
Article
Affiliation country: