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Dominant Driving Forces in Human Telomere Quadruplex Binding-Induced Structural Alterations

Bončina, M; Hamon, F; Islam, B; Teulade-Fichou, MP; Vesnaver, G; Haider, S; Lah, J; (2015) Dominant Driving Forces in Human Telomere Quadruplex Binding-Induced Structural Alterations. Biophysical Journal , 108 (12) pp. 2903-2911. 10.1016/j.bpj.2015.05.001. Green open access

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Abstract

Recently various pathways of human telomere (ht) DNA folding into G-quadruplexes and of ligand binding to these structures have been proposed. However, the key issue as to the nature of forces driving the folding and recognition processes remains unanswered. In this study, structural changes of 22-mer ht-DNA fragment (Tel22), induced by binding of ions (K(+), Na(+)) and specific bisquinolinium ligands, were monitored by calorimetric and spectroscopic methods and by gel electrophoresis. Using the global model analysis of a wide variety of experimental data, we were able to characterize the thermodynamic forces that govern the formation of stable Tel22 G-quadruplexes, folding intermediates, and ligand-quadruplex complexes, and then predict Tel22 behavior in aqueous solutions as a function of temperature, salt concentration, and ligand concentration. On the basis of the above, we believe that our work sets the framework for better understanding the heterogeneity of ht-DNA folding and binding pathways, and its structural polymorphism.

Type: Article
Title: Dominant Driving Forces in Human Telomere Quadruplex Binding-Induced Structural Alterations
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bpj.2015.05.001
Publisher version: http://dx.doi.org/10.1016/j.bpj.2015.05.001
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/1470024
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