title: p53 binds human telomeric G-quadruplex in vitro.
abstract: The tumor suppressor protein p53 is a key factor in genome stability and one of the most studied of DNA binding proteins. This is the first study on the interaction of wild-type p53 with guanine quadruplexes formed by the human telomere sequence. Using electromobility shift assay and ELISA, we show that p53 binding to telomeric G-quadruplexes increases with the number of telomeric repeats. Further, p53 strongly favors G-quadruplexes folded in potassium over those formed in sodium, thus indicating the telomeric G-quadruplex conformational selectivity of p53. The presence of the quadruplex-stabilizing ligand, N-methyl mesoporphyrin IX (NMM), increases p53 recognition of G-quadruplexes in potassium. Using deletion mutants and selective p53 core domain oxidation, both p53 DNA binding domains are shown to be crucial for telomeric G-quadruplex recognition.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Matej
authors.initials: M
authors.lastname: Adámik
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Iva
authors.initials: I
authors.lastname: Kejnovská
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Pavla
authors.initials: P
authors.lastname: Bažantová
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Petr
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Renčiuk
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Vorlíčková
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, CZ-612 65 Brno, Czech Republic. Electronic address: maruska@ibp.cz.
authors.forename: Marie
authors.initials: M
authors.lastname: Brázdová
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D054856:G-Quadruplexes; D006801:Humans; D008652:Mesoporphyrins / Q000737:chemistry; D009154:Mutation; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011188:Potassium / Q000737:chemistry; D011485:Protein Binding; D020080:Tandem Repeat Sequences / Q000235:genetics; D016615:Telomere / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D008652:Mesoporphyrins; D009841:Oligonucleotides; D016159:Tumor Suppressor Protein p53; C065420:N-methylmesoporphyrin IX; D004247:DNA; D011188:Potassium
keywords: DNA-protein interaction; G-quadruplex; Telomere DNA; p53 protein