Destabilizing Interactions in Human Telomeric G‑Quadruplex Multimers
Luca Bertini, Mattia Trapella, Deniz Mostarac, Valeria Libera, Caterina Petrillo, Cristiano De Michele, Lucia Comez, Alessandro Paciaroni

TL;DR
This paper explores how G-Quadruplex structures in human telomeres interact and destabilize each other, affecting their arrangement and biological function.
Contribution
The study introduces a helix–coil model to describe stacking–unstacking equilibrium in G-Quadruplex multimers using simulations and analytical methods.
Findings
Significant destabilizing interactions between G-Quadruplexes reduce stacked conformations.
A helix–coil model predicts stacked and unstacked G-Quadruplex multiplets in long sequences.
Abstract
G-Quadruplexes are secondary structures that may form in G-rich nucleic acid sequences. The extended overhang at the ends of human telomeres has the potential to form multiple G-Quadruplexes that are crucial in regulating key biological processes. Here, we employ small-angle X-ray scattering-guided extremely coarse-grained simulations to provide a picture of the arrangement of G-Quadruplexes in long telomeric sequences. We observe significant destabilizing interactions between G-Quadruplexes, thus making the stacked conformation less prevalent. A helix–coil model is proposed to analytically describe the stacking–unstacking equilibrium within G-Quadruplex multimers and predict the occurrence of stacked and unstacked G-Quadruplex multiplets in arbitrarily long sequences.
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
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Taxonomy
TopicsAdvanced biosensing and bioanalysis techniques · DNA and Nucleic Acid Chemistry · RNA Interference and Gene Delivery
