1. p53 binds human telomeric G-quadruplex in vitro.
- Author
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Adámik M, Kejnovská I, Bažantová P, Petr M, Renčiuk D, Vorlíčková M, and Brázdová M
- Subjects
- Base Sequence, Binding Sites genetics, Binding, Competitive, Circular Dichroism, DNA genetics, DNA metabolism, Electrophoretic Mobility Shift Assay, Enzyme-Linked Immunosorbent Assay, Humans, Mesoporphyrins chemistry, Mutation, Oligonucleotides chemistry, Oligonucleotides genetics, Oligonucleotides metabolism, Potassium chemistry, Protein Binding, Tandem Repeat Sequences genetics, Telomere genetics, Telomere metabolism, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, DNA chemistry, G-Quadruplexes, Telomere chemistry, Tumor Suppressor Protein p53 chemistry
- 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., (Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)
- Published
- 2016
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