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Structural diversity of supercoiled DNA

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  • Rossitza N. Irobalieva

    (Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 77030 USA
    Baylor College of Medicine, Houston, Texas 77030 USA)

  • Jonathan M. Fogg

    (Baylor College of Medicine, Houston, Texas 77030 USA
    Baylor College of Medicine
    Baylor College of Medicine)

  • Daniel J. Catanese

    (Baylor College of Medicine, Houston, Texas 77030 USA
    Baylor College of Medicine
    Baylor College of Medicine)

  • Thana Sutthibutpong

    (School of Physics and Astronomy, University of Leeds)

  • Muyuan Chen

    (Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 77030 USA
    Baylor College of Medicine, Houston, Texas 77030 USA)

  • Anna K. Barker

    (Baylor College of Medicine)

  • Steven J. Ludtke

    (Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 77030 USA
    Baylor College of Medicine, Houston, Texas 77030 USA)

  • Sarah A. Harris

    (School of Physics and Astronomy, University of Leeds)

  • Michael F. Schmid

    (Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 77030 USA
    Baylor College of Medicine, Houston, Texas 77030 USA)

  • Wah Chiu

    (Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 77030 USA
    Baylor College of Medicine, Houston, Texas 77030 USA
    Baylor College of Medicine)

  • Lynn Zechiedrich

    (Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 77030 USA
    Baylor College of Medicine, Houston, Texas 77030 USA
    Baylor College of Medicine
    Baylor College of Medicine)

Abstract

By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA minicircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function.

Suggested Citation

  • Rossitza N. Irobalieva & Jonathan M. Fogg & Daniel J. Catanese & Thana Sutthibutpong & Muyuan Chen & Anna K. Barker & Steven J. Ludtke & Sarah A. Harris & Michael F. Schmid & Wah Chiu & Lynn Zechiedri, 2015. "Structural diversity of supercoiled DNA," Nature Communications, Nature, vol. 6(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9440
    DOI: 10.1038/ncomms9440
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    Cited by:

    1. Meng Zhang & César Díaz-Celis & Jianfang Liu & Jinhui Tao & Paul D. Ashby & Carlos Bustamante & Gang Ren, 2024. "Angle between DNA linker and nucleosome core particle regulates array compaction revealed by individual-particle cryo-electron tomography," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Serena Renzi & Luca Digiacomo & Daniela Pozzi & Erica Quagliarini & Elisabetta Vulpis & Maria Valeria Giuli & Angelica Mancusi & Bianca Natiello & Maria Gemma Pignataro & Gianluca Canettieri & Laura M, 2024. "Structuring lipid nanoparticles, DNA, and protein corona into stealth bionanoarchitectures for in vivo gene delivery," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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