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Inhibited complete folding of consecutive human telomeric G-quadruplexes.

Emil Laust Kristoffersen1, Andrea Coletta2, Line Mørkholt Lund1

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This summary is machine-generated.

Human G-quadruplex DNA folding is complex, with many structures forming but slow equilibrium. Full folding requires unfolding off-path conformations, showing it

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Area of Science:

  • Molecular Biology
  • Biophysics
  • Genomics

Background:

  • Noncanonical DNA structures called G-quadruplexes are vital in human DNA metabolism.
  • The telomeric overhang region, associated with cancer and aging, contains G-rich repeats prone to G-quadruplex formation.
  • Multiple consecutive G-quadruplexes can form in specific genomic regions.

Purpose of the Study:

  • To investigate the folding dynamics of consecutive G-quadruplexes.
  • To understand the influence of different ionic conditions (potassium and sodium) on G-quadruplex formation.
  • To elucidate the factors inhibiting complete G-quadruplex folding.

Main Methods:

  • Single-molecule Förster Resonance Energy Transfer (smFRET) spectroscopy
  • Circular dichroism (CD) spectroscopy
  • Thermal melting analysis
  • Molecular dynamics (MD) simulations

Main Results:

  • Observed coexistence of partially and fully folded DNA structures, including consecutive G-quadruplexes.
  • Demonstrated fast G-quadruplex folding but slow thermodynamic equilibrium establishment in sodium buffers.
  • Identified inhibition of full consecutive G-quadruplex formation by off-path DNA conformations.

Conclusions:

  • Consecutive G-quadruplex formation can be described by a unified model under non-equilibrium and equilibrium conditions.
  • The numerous possible DNA conformations can hinder the achievement of fully folded consecutive G-quadruplex structures.
  • Understanding these folding pathways is crucial for G-quadruplex-related biological processes.