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Involvement of G-quadruplex regions in mammalian replication origin activity.

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Prorok, Paulina 
Artufel, Marie 
Aze, Antoine 
Coulombe, Philippe 
Peiffer, Isabelle 


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.



Animals, Cells, Cultured, DNA Replication, G-Quadruplexes, Genetic Vectors, Humans, Mammals, Mice, Mutation, NIH 3T3 Cells, Oocytes, Plasmids, Replication Origin, Xenopus laevis

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Nat Commun

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Springer Science and Business Media LLC