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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.

Original publication

DOI

10.1074/jbc.M005962200

Type

Journal article

Journal

J Biol Chem

Publication Date

16/02/2001

Volume

276

Pages

4640 - 4646

Keywords

Animals, Anthracenes, DNA, GC Rich Sequence, Genes, myc, Humans, Models, Genetic, Mutation, Nucleic Acid Conformation, Nucleic Acid Heteroduplexes, Oxytricha, Perylene, Piperidines, Promoter Regions, Genetic, Telomere