The major G-quadruplex formed in the human platelet-derived growth factor receptor β promoter adopts a novel broken-strand structure in K+ solution

Yuwei Chen, Prashansa Agrawal, Robert V. Brown, Emmanuel Hatzakis, Laurence Hurley, Danzhou Yang

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Overexpression of platelet-derived growth factor receptor β (PDGFR-β) has been associated with cancers and vascular and fibrotic disorders. PDGFR-β has become an attractive target for the treatment of cancers and fibrotic disorders. DNA G-quadruplexes formed in the GC-rich nuclease hypersensitivity element of the human PDGFR-β gene promoter have been found to inhibit PDGFR-β transcriptional activity. Here we determined the major G-quadruplex formed in the PDGFR-β promoter. Instead of using four continuous runs with three or more guanines, this G-quadruplex adopts a novel folding with a broken G-strand to form a primarily parallel-stranded intramolecular structure with three 1 nucleotide (nt) double-chain-reversal loops and one additional lateral loop. The novel folding of the PDGFR-β promoter G-quadruplex emphasizes the robustness of parallel-stranded structural motifs with a 1 nt loop. Considering recent progress on G-quadruplexes formed in gene-promoter sequences, we suggest the 1 nt looped GiNGj motif may have been evolutionarily selected to serve as a stable foundation upon which the promoter G-quadruplexes can build. The novel folding of the PDGFR-β promoter G-quadruplex may be attractive for small-molecule drugs that specifically target this secondary structure and modulate PDGFR-β gene expression.

Original languageEnglish (US)
Pages (from-to)13220-13223
Number of pages4
JournalJournal of the American Chemical Society
Volume134
Issue number32
DOIs
StatePublished - Aug 15 2012

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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