Structure of the biologically relevant g-quadruplex in the c-MYC promoter

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Abstract

The nuclease hypersensitivity element III1 (NHE III1) in the c-MYC promoter controls up to 80-90% of the transcriptional activity of this gene. We have demonstrated that the guanine-rich strand of the NHE III 1 forms a G-quadruplex consisting of a mixture of four biologically relevant loop isomers that function as a silencer element. NMR studies have shown that these G-quadruplexes are propeller-type parallel structures consisting of three stacked G-tetrads and three double-chain reversal loops. An NMR-derived solution structure for this quadruplex provides insight into the unusual stability of the structure. This structure is a target for small molecule inhibitors of c-MYC gene expression.

Original languageEnglish (US)
Pages (from-to)951-968
Number of pages18
JournalNucleosides, Nucleotides and Nucleic Acids
Volume25
Issue number8
DOIs
StatePublished - Sep 1 2006

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Keywords

  • G-quadruplex
  • Transcriptional control
  • c-MYC

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Genetics

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