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ACS Chem Biol. 2019 Sep 20;14(9):1951-1963. doi: 10.1021/acschembio.9b00428. Epub 2019 Sep 5.

GTP-Dependent Formation of Multimeric G-Quadruplexes.

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Institute of Organic Chemistry and Biochemistry ASCR , Prague 166 10 , Czech Republic.
Department of Biochemistry and Microbiology , University of Chemistry and Technology , Prague 166 28 , Czech Republic.
Cancer Center and Department of Pathology, Massachusetts General Hospital , Harvard Medical School , Boston , Massachusetts 02114 , United States.
Department of Cell Biology , Charles University in Prague , Faculty of Science, Prague 128 44 , Czech Republic.


G-Quadruplexes are noncanonical nucleic acid structures made up of stacked guanosine tetrads connected by short loops. They are frequently used building blocks in synthetic biology and thought to play widespread biological roles. Multimerization can change the functional properties of G-quadruplexes, and understanding the factors that modulate this process remains an important goal. Here, we report the discovery of a novel mechanism by which the formation of multimeric G-quadruplexes can be controlled using GTP. We show that GTP likely inhibits multimer formation by becoming incorporated into a tetrad in the monomeric form of the structure and define the sequence requirements of G-quadruplexes that form GTP-dependent structures. These experiments provide new insights into the small molecule control of G-quadruplex multimerization. They also suggest possible roles for GTP-dependent multimeric G-quadruplexes in both synthetic and natural biological systems.


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