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Deciphering High-Resolution 3D Chromatin Organization via Capture Hi-C
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High-resolution insight into G-overhang architecture.

Robert Hänsel1, Frank Löhr, Lukáš Trantirek

  • 1Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt/Main, Germany. rhaensel.bpc@gmail.com

Journal of the American Chemical Society
|January 24, 2013
PubMed
Summary

Intracellular molecular crowding influences telomeric G-quadruplex (G4) DNA folding. Dilute solutions mimic physiological conditions, revealing G4 DNA adopts hybrid-1 and parallel propeller structures.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Telomeric G-quadruplex (G4) DNA structures play crucial roles in chromosome stability.
  • Understanding G4 DNA folding under physiological conditions is vital for comprehending cellular processes.
  • Intracellular molecular crowding and hydration significantly impact nucleic acid structures.

Purpose of the Study:

  • To investigate the effect of intracellular molecular crowding and hydration on a model telomeric G-quadruplex (G4) DNA structure.
  • To elucidate the conformational preferences of G4 DNA under various solution conditions, including those mimicking the cellular environment.
  • To provide high-resolution structural insights into telomeric G-overhang architecture.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy.
  • Fluorescence spectroscopy.
  • Site-specific (15)N labeling of G4 DNA units.

Main Results:

  • The telomeric G-quadruplex d(AG(3)(TTAGGG)(3)) adopted a hybrid-1 conformation in dilute potassium-based solutions, mimicking in vivo conditions.
  • In water-depleted solutions, modeling molecular crowding, the parallel propeller fold was observed.
  • High-resolution NMR revealed coexistence of 2-tetrad antiparallel basket and hybrid-2 structures in a "beads-on-a-string" arrangement under near-physiological conditions.

Conclusions:

  • Dilute potassium-based solutions effectively model the cellular environment for telomeric G4 DNA folding.
  • The 2-tetrad antiparallel basket and hybrid-2 topologies are identified as key structures of telomeric G-overhangs under physiological conditions.
  • These identified structures serve as potential targets for developing telomere-specific G4 ligands.