title: Double stranded promoter region of BRAF undergoes to structural rearrangement in nearly physiological conditions.
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.
authors.affiliation: Dept. of Pharmaceutical and Pharmacological Sciences, v. Marzolo 5, 35131 PD, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Greco
authors.affiliation: Dept. of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, Milano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Folini
authors.affiliation: Dept. of Pharmaceutical and Pharmacological Sciences, v. Marzolo 5, 35131 PD, Italy. Electronic address: claudia.sissi@unipd.it.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sissi
mesh_terms: D002942:Circular Dichroism; D024202:Electrophoretic Mobility Shift Assay; D054856:G-Quadruplexes; D020862:GC Rich Sequence; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D059372:Nucleotide Motifs; D009994:Osmolar Concentration; D011092:Polyethylene Glycols / Q000737:chemistry; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013501:Surface-Active Agents / Q000737:chemistry; D044366:Transition Temperature
chemical_list: D013501:Surface-Active Agents; D011092:Polyethylene Glycols; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; G-quadruplex; Oncogene; i-motif