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Involvement of G-quadruplex Regions in Mammalian Replication Origin Activity

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, etc.

Nat Commun. 2019 Jul 22;10(1):3274.

PMID: 31332171

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP929895454	PhenDC3		929895-45-4	Price

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