Induction of Duplex to G-quadruplex Transition in the c-myc Promoter Region by a Small Molecule

Anupama Rangan, Oleg Yu Fedoroff, Laurence H. Hurley

Research output: Contribution to journalArticle

164 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4640-4646
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number7
DOIs
StatePublished - Feb 16 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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