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Involvement of G-quadruplex regions in mammalian replication origin activity

Author

Listed:
  • Paulina Prorok

    (CNRS-University of Montpellier)

  • Marie Artufel

    (Aix Marseille Univ, INSERM, TAGC)

  • Antoine Aze

    (CNRS-University of Montpellier)

  • Philippe Coulombe

    (CNRS-University of Montpellier)

  • Isabelle Peiffer

    (CNRS-University of Montpellier)

  • Laurent Lacroix

    (University of Cambridge)

  • Aurore Guédin

    (ARNA Laboratory, Université de Bordeaux, Inserm U1212, CNRS UMR5320, Institut Européen de Chimie Biologie (IECB))

  • Jean-Louis Mergny

    (ARNA Laboratory, Université de Bordeaux, Inserm U1212, CNRS UMR5320, Institut Européen de Chimie Biologie (IECB)
    Institut Curie, CNRS UMR9187, Inserm U1196, Universite Paris Saclay)

  • Julia Damaschke

    (German Research Center for Environmental Health)

  • Aloys Schepers

    (German Research Center for Environmental Health
    Institute for Diabetes and Obesity, Helmholtz Zentrum München, Ingolstädter Landstrasse)

  • Christelle Cayrou

    (CNRS-University of Montpellier
    Centre de Recherche en Cancérologie de Marseille 27 Boulevard Lei Roure)

  • Marie-Paule Teulade-Fichou

    (Campus Universitaire)

  • Benoit Ballester

    (Aix Marseille Univ, INSERM, TAGC)

  • Marcel Méchali

    (CNRS-University of Montpellier)

Abstract

Genome-wide studies of DNA replication origins revealed that origins preferentially associate with an Origin G-rich Repeated Element (OGRE), potentially forming G-quadruplexes (G4). Here, we functionally address their requirements for DNA replication initiation in a series of independent approaches. Deletion of the OGRE/G4 sequence strongly decreased the corresponding origin activity. Conversely, the insertion of an OGRE/G4 element created a new replication origin. This element also promoted replication of episomal EBV vectors lacking the viral origin, but not if the OGRE/G4 sequence was deleted. A potent G4 ligand, PhenDC3, stabilized G4s but did not alter the global origin activity. However, a set of new, G4-associated origins was created, whereas suppressed origins were largely G4-free. In vitro Xenopus laevis replication systems showed that OGRE/G4 sequences are involved in the activation of DNA replication, but not in the pre-replication complex formation. Altogether, these results converge to the functional importance of OGRE/G4 elements in DNA replication initiation.

Suggested Citation

  • Paulina Prorok & Marie Artufel & Antoine Aze & Philippe Coulombe & Isabelle Peiffer & Laurent Lacroix & Aurore Guédin & Jean-Louis Mergny & Julia Damaschke & Aloys Schepers & Christelle Cayrou & Marie, 2019. "Involvement of G-quadruplex regions in mammalian replication origin activity," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11104-0
    DOI: 10.1038/s41467-019-11104-0
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    Cited by:

    1. Anna C. Papageorgiou & Michaela Pospisilova & Jakub Cibulka & Raghib Ashraf & Christopher A. Waudby & Pavel Kadeřávek & Volha Maroz & Karel Kubicek & Zbynek Prokop & Lumir Krejci & Konstantinos Tripsi, 2023. "Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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