Unraveling the Thermodynamics of the Folding and Interconversion of Human Telomere G‐Quadruplexes

Abstract

AbstractWhy human telomere DNA fragments fold into different G‐quadruplex structures with parallel, hybrid, and antiparallel strand orientations depending on the temperature and concentration of co‐solutes remains poorly understood. Similarly, the formation of intermediate structures along the folding or interconversion pathways is not well understood. Herein, we address these questions by introducing a conceptual framework, based on the global thermodynamic analysis of DSC and CD spectroscopy data, which led to a detailed description of the topological phase space (phase diagram) of the stability of the human telomere fragment 5′‐AGGG(TTAGGG)3‐3′ (Tel22). This framework clarifies the driving forces of quadruplex folding and interconversion processes over a wide range of temperatures and ion (K+, Na+) and polyethylene glycol (PEG) concentrations and demonstrates their linkage to the human telomere DNA structural features.