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Updated: Jul 10, 2025
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A G-quadruplex DNA-affinity Approach for Purification of Enzymatically Active G4 Resolvase1
Published on: March 18, 2017
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A sodium/potassium switch for G4-prone G/C-rich sequences
Yu Luo1,2, Martina Lenarčič Živković3,4, Jiawei Wang1
1Laboratoire d'Optique et Biosciences, Ecole Polytechnique, CNRS, Inserm, Institut Polytechnique de Paris, 91128 Palaiseau, France.
Nucleic Acids Research
|November 21, 2023
Summary
Changes in sodium/potassium ([Na+]/[K+]) ratios influence G-quadruplex (G4) structures. Cytosines in G4 loops increase the likelihood of alternative structures, impacting cellular responses to ionic shifts.
Area of Science:
- Biochemistry
- Genomics
- Molecular Biology
Background:
- Metal ions are vital for life, with differing intracellular and extracellular concentrations.
- G-quadruplexes (G4s) are ion-dependent DNA structures sensitive to ionic environment changes, particularly the [Na+]/[K+] ratio.
- The human genome contains numerous G/C-rich sequences with the potential to form G4s or competing hairpin structures.
Purpose of the Study:
- To investigate the impact of the [Na+]/[K+] ratio on the structural preferences of G/C-rich sequences.
- To understand how cytosine presence in G-quadruplex loops affects folding and stability.
- To explore the dynamic structural changes in response to varying ionic conditions.
Main Methods:
- Utilized a model G4 sequence (CEBwt) with a 9-nt central loop.
- Systematically introduced cytosines into the CEBwt loop to create a series of mutations.
- Employed Nuclear Magnetic Resonance (NMR) spectroscopy to analyze structural folding in vitro and in cellular contexts.
Main Results:
- Cytosine incorporation into G4 loops did not impede G4 folding or reduce stability.
- Increased cytosine content enhanced the probability of forming competing hairpin or intermolecular duplex structures.
- Observed slow G4 formation in vitro (potassium-rich conditions) and in cells, indicating delayed kinetics.
Conclusions:
- G/C-rich sequences exhibit 'shape-shifting' capabilities, dynamically altering structure based on [Na+]/[K+] ratios.
- The presence of cytosines in G4 loops promotes structural plasticity and responsiveness to ionic fluctuations.
- These findings highlight the complex interplay between DNA sequence, ionic environment, and structural dynamics in biological systems.
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