Double stranded promoter region of BRAF undergoes to structural rearrangement in nearly physiological conditions

FEBS Lett. 2015 Jul 22;589(16):2117-23. doi: 10.1016/j.febslet.2015.06.025. Epub 2015 Jul 2.

Abstract

The folding of oncogene promoters into non-canonical DNA secondary structures is considered a strategy to control gene expression. Herein, we focused on a 30 bases sequence located upstream of the transcription start site of BRAF (Braf-176) that contains 80% of guanines. We analyzed the structural behavior of the G- and C-rich strands. By the use of spectroscopic and electrophoretic techniques we confirmed that they actually fold into a predominant antiparallel G-quadruplex and into an i-motif, respectively, and that they can coexist at nearly physiological conditions. Finally, the influence of several factors (KCl, pH, PEG₂₀₀) on the conversion of the double stranded form of the oncogene promoter into the two above mentioned non-canonical structures has been explored.

Keywords: BRAF; G-quadruplex; Oncogene; i-motif.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • Electrophoretic Mobility Shift Assay
  • G-Quadruplexes
  • GC Rich Sequence*
  • Humans
  • Hydrogen-Ion Concentration
  • Models, Molecular*
  • Nucleic Acid Conformation*
  • Nucleic Acid Denaturation
  • Nucleotide Motifs
  • Osmolar Concentration
  • Polyethylene Glycols / chemistry
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins B-raf / chemistry
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Surface-Active Agents / chemistry
  • Transition Temperature

Substances

  • Surface-Active Agents
  • Polyethylene Glycols
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf