p53 binds human telomeric G-quadruplex in vitro

• Published in: Biochimie Vol. 128-129; no. C; pp. 83 - 91
• Main Authors: Adámik, Matej, Kejnovská, Iva, Bažantová, Pavla, Petr, Marek, Renčiuk, Daniel, Vorlíčková, Michaela, Brázdová, Marie
• Format: Journal Article
• Language: English
• Published: France Elsevier B.V 01.09.2016; Elsevier
• Subjects: Base Sequence; Binding Sites - genetics; Binding, Competitive; Circular Dichroism; DNA - chemistry; DNA - genetics; DNA - metabolism; DNA-protein interaction; Electrophoretic Mobility Shift Assay; Enzyme-Linked Immunosorbent Assay; G-quadruplex; G-Quadruplexes; Humans; Mesoporphyrins - chemistry; Mutation; Oligonucleotides - chemistry; Oligonucleotides - genetics; Oligonucleotides - metabolism; p53 protein; Potassium - chemistry; Protein Binding; Tandem Repeat Sequences - genetics; Telomere - chemistry; Telomere - genetics; Telomere - metabolism; Telomere DNA; Tumor Suppressor Protein p53 - chemistry; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; DNA-protein interaction; p53 protein; G-quadruplex; Telomere DNA
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2016.07.004

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. •Binding of p53 increases with number of telomeric repeats.•p53 prefers binding to K+-stabilized over Na+-stabilized telomere G-quadruplex.•p53 binding to telomere G-quadruplexes in KCl is enhanced by folding with NMM.•p53 C-terminus aids in recognition of telomere G-quadruplexes.