Involvement of G-quadruplex regions in mammalian replication origin activity

Paulina Prorok, Marie Artufel, Antoine Aze, Philippe Coulombe, Isabelle Peiffer, Laurent Lacroix, Aurore Guédin, Jean-Louis Mergny, Julia Damaschke, Aloys Schepers, Christelle Cayrou, Marie-Paule Teulade-Fichou, Benoit Ballester () and Marcel Méchali ()
Additional contact information
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)
Julia Damaschke: German Research Center for Environmental Health
Aloys Schepers: German Research Center for Environmental Health
Christelle Cayrou: CNRS-University of Montpellier
Marie-Paule Teulade-Fichou: Campus Universitaire
Benoit Ballester: Aix Marseille Univ, INSERM, TAGC
Marcel Méchali: CNRS-University of Montpellier

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11104-0

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