期刊
NUCLEIC ACIDS RESEARCH
卷 45, 期 8, 页码 4929-4943出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkx100
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资金
- National Institutes of Health/National Cancer Institute (NIH/NCI) [CA093729]
- Cancer Prevention Research Institute of Texas (CPRIT) fellowship [IDRP140108]
- Jean Dreyfus Boissevain Lectureship for Undergraduate Institutions
- Robert A. Welch Foundation [AF-0005]
- Howard Hughes Medical Institute through the Undergraduate Science Education Program [52007558]
- NIH/NCI [CA093729]
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 (nonB 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 usingmultiple 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.
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