Abstract
A major control element of the human c-myc oncogene is the nuclease-hypersensitive purine/pyrimidine-rich sequence. This double-stranded DNA fragment, corresponding to the 27-base pair segment in the nuclease-hypersensitive element of the c-myc promoter region, forms a stable Watson-Crick double helix under physiological conditions. However, this duplex DNA can be effectively converted to G-quadruplex DNA by a small molecular weight ligand. Both intermolecular and intramolecular G-quadruplex forms can be induced by this ligand. Similar transitional changes are also observed with the duplex telomeric sequence from the Oxytricha species. These results provide additional support to the idea that G-quadruplex structures may play structural roles in vivo and also provide insight into novel methodologies for rational drug design. These structurally altered DNA elements might serve as regulatory signals in gene expression or in telomere dynamics and hence are promising targets for drug action.
Highlights
A major control element of the human c-myc oncogene is the nuclease-hypersensitive purine/pyrimidine-rich sequence
The mechanisms involved in this regulation are not yet completely understood, a major control element of the human c-myc oncogene has been localized. This is a purine/pyrimidine-rich region located 115 bases upstream from the P1 promoter, which controls up to 95% of the total c-myc transcription [3, 4]. This DNA segment is highly sensitive to DNase I and S1 nuclease [5, 6] and is termed the nuclease-hypersensitive element (NHE)
Structural variations in the NHE can influence the binding of transcription factors
Summary
A major control element of the human c-myc oncogene is the nuclease-hypersensitive purine/pyrimidine-rich sequence. In this study we demonstrate that a small molecule such as PIPER can facilitate the formation of G-quadruplex structures from G-rich single-stranded DNA and from the Watson-Crick base-paired G-rich duplex DNA.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
