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Direct and Single-Molecule Visualization of the Solution-State Structures of G-Hairpin and G-Triplex Intermediates

Authors

  • Dr. Arivazhagan Rajendran,

    1. Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8502 (Japan)
    2. Current address: Faculty of Medicine and Life Science Center of TARA, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki-ken 305-8577 (Japan)
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  • Prof. Dr. Masayuki Endo,

    Corresponding author
    1. Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-ushinomiyacho, Sakyo-ku, Kyoto 606-8501 (Japan)
    2. CREST, Japan Science and Technology Corporation (JST), Sanbancho, Chiyoda-ku, Tokyo 102-0075 (Japan)
    • Masayuki Endo, Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-ushinomiyacho, Sakyo-ku, Kyoto 606-8501 (Japan)

      Hiroshi Sugiyama, Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8502 (Japan)

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  • Kumi Hidaka,

    1. Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8502 (Japan)
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  • Prof. Dr. Hiroshi Sugiyama

    Corresponding author
    1. Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8502 (Japan)
    2. Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-ushinomiyacho, Sakyo-ku, Kyoto 606-8501 (Japan)
    3. CREST, Japan Science and Technology Corporation (JST), Sanbancho, Chiyoda-ku, Tokyo 102-0075 (Japan)
    • Masayuki Endo, Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-ushinomiyacho, Sakyo-ku, Kyoto 606-8501 (Japan)

      Hiroshi Sugiyama, Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8502 (Japan)

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  • This work was supported by Core Research for Evolutional Science and Technology (CREST) of JST and JSPS KAKENHI (Grant Numbers 24310097, 24225005, 24104002). Financial support from The Mitsubishi Foundation and The Asahi Glass Foundation to M.E. are also acknowledged. A.R. expresses sincere thanks to JSPS for the Postdoctoral fellowship.

Abstract

We present the direct and single-molecule visualization of the in-pathway intermediates of the G-quadruplex folding that have been inaccessible by any experimental method employed to date. Using DNA origami as a novel tool for the structural control and high-speed atomic force microscopy (HS-AFM) for direct visualization, we captured images of the unprecedented solution-state structures of a tetramolecular antiparallel and (3+1)-type G-quadruplex intermediates, such as G-hairpin and G-triplex, with nanometer precision. No such structural information was reported previously with any direct or indirect technique, solution or solid-state, single-molecule or bulk studies, and at any resolution. Based on our results, we proposed a folding mechanism of these G-quadruplexes.

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