title: Dominant Driving Forces in Human Telomere Quadruplex Binding-Induced Structural Alterations.
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.
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Matjaž
authors.initials: M
authors.lastname: Bončina
authors.affiliation: Institut Curie, Centre National de la Recherche Scientifique UMR-176, Centre Universitaire d'Orsay, Orsay, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Hamon
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University of Belfast, Belfast, UK.
authors.forename: Barira
authors.initials: B
authors.lastname: Islam
authors.affiliation: Institut Curie, Centre National de la Recherche Scientifique UMR-176, Centre Universitaire d'Orsay, Orsay, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Teulade-Fichou
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Gorazd
authors.initials: G
authors.lastname: Vesnaver
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University of Belfast, Belfast, UK; University College London School of Pharmacy, Bloomsbury, London, UK.
authors.forename: Shozeb
authors.initials: S
authors.lastname: Haider
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia. Electronic address: jurij.lah@fkkt.uni-lj.si.
authors.forename: Jurij
authors.initials: J
authors.lastname: Lah
mesh_terms: D054856:G-Quadruplexes; D006801:Humans; D056004:Molecular Dynamics Simulation; D011188:Potassium / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D016615:Telomere / Q000737:chemistry*
chemical_list: D012964:Sodium; D011188:Potassium