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Nat Commun January 1, 2019; 10 (1): 3274.

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

Prorok P , Artufel M , Aze A , Coulombe P , Peiffer I , Lacroix L , Guédin A , Mergny JL , Damaschke J , Schepers A , Cayrou C , Teulade-Fichou MP , Ballester B , Méchali M .

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.

PubMed ID: 31332171
PMC ID: PMC6646384
Article link: Nat Commun

Genes referenced: actb h2bc21 ids kidins220 rai1

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