A. Rangan et al., Induction of duplex to G-quadruplex transition in the c-myc promoter region by a small molecule, J BIOL CHEM, 276(7), 2001, pp. 4640-4646
A major control element of the human c-myc oncogene is the nuclease-hyperse
nsitive purine/pyrimidine-rich sequence. This double-stranded DNA fragment,
corresponding to the 27-base pair segment in the nuclease-hypersensitive e
lement of the c-myc promoter region, forms a stable Watson-Crick double hel
ix under physiological conditions. However, this duplex DNA can be effectiv
ely 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 tel
omeric sequence from the Oxytricha species. These results provide additiona
l support to the idea that G-quadruplex structures may play structural role
s in vivo and also provide insight into novel methodologies for rational dr
ug design. These structurally altered DNA elements might serve as regulator
y signals in gene expression or in telomere dynamics and hence are promisin
g targets for drug action.