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Transient Hoogsteen base pairs in canonical duplex DNA

Author

Listed:
  • Evgenia N. Nikolova

    (University of Michigan, 930 North University Avenue)

  • Eunae Kim

    (University of California, Natural Sciences 2, Irvine, California 92697, USA)

  • Abigail A. Wise

    (University of Michigan, 930 North University Avenue)

  • Patrick J. O’Brien

    (University of Michigan)

  • Ioan Andricioaei

    (University of California, Natural Sciences 2, Irvine, California 92697, USA)

  • Hashim M. Al-Hashimi

    (University of Michigan, 930 North University Avenue)

Abstract

Sequence-directed variations in the canonical DNA double helix structure that retain Watson–Crick base-pairing have important roles in DNA recognition, topology and nucleosome positioning. By using nuclear magnetic resonance relaxation dispersion spectroscopy in concert with steered molecular dynamics simulations, we have observed transient sequence-specific excursions away from Watson–Crick base-pairing at CA and TA steps inside canonical duplex DNA towards low-populated and short-lived A•T and G•C Hoogsteen base pairs. The observation of Hoogsteen base pairs in DNA duplexes specifically bound to transcription factors and in damaged DNA sites implies that the DNA double helix intrinsically codes for excited state Hoogsteen base pairs as a means of expanding its structural complexity beyond that which can be achieved based on Watson–Crick base-pairing. The methods presented here provide a new route for characterizing transient low-populated nucleic acid structures, which we predict will be abundant in the genome and constitute a second transient layer of the genetic code.

Suggested Citation

  • Evgenia N. Nikolova & Eunae Kim & Abigail A. Wise & Patrick J. O’Brien & Ioan Andricioaei & Hashim M. Al-Hashimi, 2011. "Transient Hoogsteen base pairs in canonical duplex DNA," Nature, Nature, vol. 470(7335), pages 498-502, February.
    • Handle: RePEc:nat:nature:v:470:y:2011:i:7335:d:10.1038_nature09775
    DOI: 10.1038/nature09775
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    Cited by:

    1. Fang-Chieh Chou & Jan Lipfert & Rhiju Das, 2014. "Blind Predictions of DNA and RNA Tweezers Experiments with Force and Torque," PLOS Computational Biology, Public Library of Science, vol. 10(8), pages 1-19, August.
    2. Ge Han & Yi Xue, 2022. "Rational design of hairpin RNA excited states reveals multi-step transitions," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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