Light rare earth elements stabilize G-quadruplex structure in variants of human telomeric sequences

Area of Science:

• Biochemistry
• Materials Science
• Genetics

Background:

• Light rare earth elements (LREEs) are increasingly vital in technology.
• Understanding LREEs' biological interactions is crucial due to potential biomacromolecular effects.

Purpose of the Study:

• To investigate the formation of G-quadruplex structures in human telomeric variants induced by LREEs.
• To elucidate the binding interactions and structural consequences of LREEs with telomeric DNA.

Main Methods:

• Thermal melting analysis to study G-quadruplex stability.
• Isothermal titration calorimetry, UV-vis, and Circular Dichroism (CD) spectroscopy to analyze binding.
• Investigated competitive binding with Na+ and K+.

Main Results:

• First discovery of LREE-induced G-quadruplex formation in human telomeric variants at micromolar concentrations.
• LREEs exhibit a 2:1 binding stoichiometry with telomeric variants, coordinating between G-quartets and on loops.
• LREE-induced G-quadruplexes adopt an antiparallel orientation; LREEs displace Na+ and K+.
• Thymine in the central loop stabilizes the LREE-induced G-quadruplex.

Conclusions:

• LREEs can induce and stabilize specific G-quadruplex structures in human telomeric DNA.
• The binding mechanism involves coordination and displacement of other cations, leading to conformational changes.
• This highlights a novel interaction of LREEs with biologically relevant DNA structures.