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DNA guanine quadruplexes: When less is more.

Helena Kašparová1, Petr Stadlbauer2, Martin Gajarský3

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International Journal of Biological Macromolecules
|January 24, 2026
PubMed
Summary
This summary is machine-generated.

Guanine quadruplexes (G4) with longer G-tracts do not increase stability. Instead, they get trapped in intermediate structures, limiting their regulatory potential in cellular processes.

Keywords:
Circular dichroism spectroscopyDNA guanine quadruplexMolecular dynamics

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Area of Science:

  • Molecular Biology
  • Genomics
  • Biophysics

Background:

  • Guanine quadruplexes (G4) are crucial nucleic acid structures regulating cellular processes.
  • The relationship between primary sequence and G4 structure is complex, especially for longer G-tracts.
  • Potential quadruplex-forming sequences (PQS) can exhibit tract sliding and conformational polymorphism.

Purpose of the Study:

  • To investigate the stability of DNA G4s with increasing G-tract lengths.
  • To understand how G-tract length affects G4 formation and stability.
  • To explore the kinetic and thermodynamic factors influencing G4 structures.

Main Methods:

  • Computational analysis of PQS.
  • Biophysical characterization of G4 structures.
  • Biochemical assays to assess G4 stability and formation.

Main Results:

  • Extending G-tracts beyond three guanines did not increase G4 stability.
  • PQS with longer G-tracts formed kinetically trapped three-tetrad intermediates.
  • Thermodynamically, antiparallel G4s outcompeted parallel four-tetrad structures.

Conclusions:

  • Longer G-tracts do not enhance G4 stability in relevant cellular timescales.
  • G4 structures with extended G-tracts may exhibit increased conformational flexibility.
  • This flexibility could enhance the regulatory potential of PQS despite kinetic limitations.