A G-rich sequence within the c-kit oncogene promoter forms a parallel G-quadruplex having asymmetric G-tetrad dynamics

J Am Chem Soc. 2009 Sep 23;131(37):13399-409. doi: 10.1021/ja904007p.

Abstract

Guanine-rich DNA sequences with the ability to form quadruplex structures are enriched in the promoter regions of protein-coding genes, particularly those of proto-oncogenes. G-quadruplexes are structurally polymorphic and their folding topologies can depend on the sample conditions. We report here on a structural study using solution state NMR spectroscopy of a second G-quadruplex-forming motif (c-kit2) that has been recently identified in the promoter region of the c-kit oncogene. In the presence of potassium ions, c-kit2 exists as an ensemble of structures that share the same parallel-stranded propeller-type conformations. Subtle differences in structural dynamics have been identified using hydrogen-deuterium exchange experiments by NMR spectroscopy, suggesting the coexistence of at least two structurally similar but dynamically distinct substates, which undergo slow interconversion on the NMR timescale.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Deuterium Exchange Measurement
  • G-Quadruplexes*
  • GC Rich Sequence*
  • Hydrogen Bonding
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Mutation
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins c-kit / genetics*

Substances

  • Proto-Oncogene Proteins c-kit