A New Pathway of DNA G-Quadruplex Formation

Authors

  • Dr. Slavko Čeru,

    1. EN-FIST Center of Excellence, Trg OF 13, 1000 Ljubljana (Slovenia)
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  • Dr. Primož Šket,

    1. EN-FIST Center of Excellence, Trg OF 13, 1000 Ljubljana (Slovenia)
    2. Slovenian NMR Center, National Institute of Chemistry, Hajdrihova 19, Ljubljana (Slovenia)
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  • Dr. Iztok Prislan,

    1. Faculty of Chemistry and Chemical Technology, Physical Chemistry, University of Ljubljana, Aškerčeva 5, Ljubljana (Slovenia)
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  • Prof. Dr. Jurij Lah,

    Corresponding author
    1. Faculty of Chemistry and Chemical Technology, Physical Chemistry, University of Ljubljana, Aškerčeva 5, Ljubljana (Slovenia)
    • Jurij Lah, Faculty of Chemistry and Chemical Technology, Physical Chemistry, University of Ljubljana, Aškerčeva 5, Ljubljana (Slovenia)===

      Janez Plavec, EN-FIST Center of Excellence, Trg OF 13, 1000 Ljubljana (Slovenia)===

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  • Prof. Dr. Janez Plavec

    Corresponding author
    1. EN-FIST Center of Excellence, Trg OF 13, 1000 Ljubljana (Slovenia)
    2. Slovenian NMR Center, National Institute of Chemistry, Hajdrihova 19, Ljubljana (Slovenia)
    3. Faculty of Chemistry and Chemical Technology, Physical Chemistry, University of Ljubljana, Aškerčeva 5, Ljubljana (Slovenia)
    • Jurij Lah, Faculty of Chemistry and Chemical Technology, Physical Chemistry, University of Ljubljana, Aškerčeva 5, Ljubljana (Slovenia)===

      Janez Plavec, EN-FIST Center of Excellence, Trg OF 13, 1000 Ljubljana (Slovenia)===

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  • This work was supported by the Slovenian Research Agency, the Ministry of Higher Education, Science and Technology of the Republic of Slovenia (grant numbers P1-0242 and J1-4020), Bio-NMR FP7 project (contract number 261863), and European Cooperation in Science and Technology (COST MP0802).

Abstract

A new folding intermediate of Oxytricha nova telomeric Oxy-1.5 G-quadruplex was characterized in aqueous solution using NMR spectroscopy, native gel electrophoresis, thermal differential spectra (TDS), CD spectroscopy, and differential scanning calorimetry (DSC). NMR experiments have revealed that this intermediate (i-Oxy-1.5) exists in two symmetric bimolecular forms in which all guanine bases are involved in GG N1-carbonyl symmetric base pairs. Kinetic analysis of K+-induced structural transitions shows that folding of Oxy-1.5 G-quadruplex from i-Oxy-1.5 is much faster and proceeds through less intermediates than folding from single strands. Therefore, a new folding pathway of Oxy-1.5 G-quadruplex is proposed. This study provides evidence that G-rich DNA sequences can self-assemble into specific pre-organized DNA structures that are predisposed to fold into G-quadruplex when interacting with cations such as potassium ions.

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