PuSH - Publication Server of Helmholtz Zentrum München: Involvement of G-quadruplex regions in mammalian replication origin activity.

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Prorok, P.* ; Artufel, M.* ; Aze, A.* ; Coulombe, P.* ; Peiffer, I.* ; Lacroix, L.* ; Guédin, A.* ; Mergny, J.L.* ; Damaschke, J. ; Schepers, A. ; Ballester, B.* ; Méchali, M.*

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

Nat. Commun. 10:3274 (2019)

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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.

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