4.8 Article

Local structure of DNA toroids reveals curvature-dependent intermolecular forces

Journal

NUCLEIC ACIDS RESEARCH
Volume 49, Issue 7, Pages 3709-3718

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab197

Keywords

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Funding

  1. CNRS
  2. French Research Agency [ANR-12-BSV5-0023]
  3. Investissements Avenir-LabEx PALM [ANR-10-LABX-0039-PALM]
  4. French Infrastructure for Integrated Structural Biology (FRISBI) [ANR-10-INBS-0]
  5. 'IDI 2016' project - IDEX Paris-Saclay [ANR-11-IDEX-0003-02]
  6. Marie Curie Integration Grant [PCIG12-GA-2012-334053]
  7. Investissements d'Avenir' LabEx PALM [ANR-10-LABX0039-PALM]
  8. ANR grant [ANR-15-CE13-0004-03]
  9. ERC Starting Grant [677532]
  10. European Research Council (ERC) [677532] Funding Source: European Research Council (ERC)

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DNA is tightly packed and curved due to polyvalent cations inducing an effective attraction. Using cryo electron microscopy, the interaction between highly curved helices was studied, revealing the dependence of helix spacing in DNA toroidal condensates on their location within the torus. This sheds light on the characteristics of the interaction potential and the softness of the interaction compared to previous bulk samples.
In viruses and cells, DNA is closely packed and tightly curved thanks to polyvalent cations inducing an effective attraction between its negatively charged filaments. Our understanding of this effective attraction remains very incomplete, partly because experimental data is limited to bulk measurements on large samples of mostly uncurved DNA helices. Here we use cryo electron microscopy to shed light on the interaction between highly curved helices. We find that the spacing between DNA helices in spermine-induced DNA toroidal condensates depends on their location within the torus, consistent with a mathematical model based on the competition between electrostatic interactions and the bending rigidity of DNA. We use our model to infer the characteristics of the interaction potential, and find that its equilibrium spacing strongly depends on the curvature of the filaments. In addition, the interaction is much softer than previously reported in bulk samples using different salt conditions. Beyond viruses and cells, our characterization of the interactions governing DNA-based dense structures could help develop robust designs in DNA nanotechnologies.

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