G4 motifs affect origin positioning and efficiency in two vertebrate replicators |
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Authors: | Anne‐Laure Valton Vahideh Hassan‐Zadeh Ingrid Lema Nicole Boggetto Patrizia Alberti Carole Saintomé Jean‐François Riou Marie‐Noëlle Prioleau |
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Institution: | 1. Institut Jacques Monod, CNRS UMR7592, Université Paris Diderot, Equipe Labellisée Ligue contre le cancer, Paris, France;2. Department of Cell and Molecular Biology, University of Tehran, Tehran, Iran;3. Faculté de Médecine Paris‐Sud, Inserm U693, Le Kremlin‐Bicêtre, France;4. Structure des Acides Nucléiques, Télomères et Evolution, Inserm U565, CNRS UMR 7196, Muséum National d'Histoire Naturelle, Université Paris 6, Paris, France |
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Abstract: | DNA replication ensures the accurate duplication of the genome at each cell cycle. It begins at specific sites called replication origins. Genome‐wide studies in vertebrates have recently identified a consensus G‐rich motif potentially able to form G‐quadruplexes (G4) in most replication origins. However, there is no experimental evidence to demonstrate that G4 are actually required for replication initiation. We show here, with two model origins, that G4 motifs are required for replication initiation. Two G4 motifs cooperate in one of our model origins. The other contains only one critical G4, and its orientation determines the precise position of the replication start site. Point mutations affecting the stability of this G4 in vitro also impair origin function. Finally, this G4 is not sufficient for origin activity and must cooperate with a 200‐bp cis‐regulatory element. In conclusion, our study strongly supports the predicted essential role of G4 in replication initiation. |
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Keywords: | cis‐regulatory element DNA replication G‐quadruplex replication origin |
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