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

Matjaž Bončina, Florian Hamon, Barira Islam, Marie Paule Teulade-Fichou, Gorazd Vesnaver, Shozeb Haider, Jurij Lah

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2903-2911
Number of pages9
JournalBiophysical Journal
Issue number12
Publication statusPublished - 16 Jun 2015
Externally publishedYes


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