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Interaction of Human Nuclear Topoisomerase I with Guanosine Quartet-forming and Guanosine-rich Single-stranded DNA and RNA Oligonucleotides

Abstract : Human nuclear DNA topoisomerase I (top1) plays a crucial role in DNA replication, transcription, and chromosome condensation. In this study, we show that intra- and intermolecular guanosine quartets (G-quartets) can inhibit top1-mediated DNA cleavage at a high affinity site. Top1-mediated DNA cleavage was also inhibited by a 16-mer single-stranded oligodeoxynucleotide (ODN) containing a G-rich sequence (G(2)T(2)G(5)TG(2)TG(3)) and by its RNA equivalent, neither of which form G-quartet structures. A comparison of various single-stranded ODN for their ability to inhibit top1-mediated DNA cleavage indicated that G-rich sequences containing repeats of 2 or 3 consecutive guanines interspaced with thymines specifically inhibited top1. We also found that both single-stranded and G-quartet-forming ODNs bind to top1 without being cleaved by the enzyme. These results demonstrate that either DNA or RNA G-rich single-stranded and G-quartet-forming oligonucleotides can bind to top1 and prevent cleavage of duplex DNA.
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https://www.hal.inserm.fr/inserm-02438310
Contributor : Philippe Pourquier <>
Submitted on : Tuesday, January 14, 2020 - 10:53:33 AM
Last modification on : Wednesday, January 15, 2020 - 1:32:59 PM

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Christophe Marchand, Philippe Pourquier, Gary Laco, Naijie Jing, Yves Pommier. Interaction of Human Nuclear Topoisomerase I with Guanosine Quartet-forming and Guanosine-rich Single-stranded DNA and RNA Oligonucleotides. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2002, 277 (11), pp.8906-8911. ⟨10.1074/jbc.M106372200⟩. ⟨inserm-02438310⟩

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