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Involvement of G-quadruplex regions in mammalian replication origin activity.
Nat. Commun. 10:3274 (2019)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Recognition Complex Binds; Dna-replication; Genome-wide; Xenopus Eggs; Initiation; Chromatin; Identification; Reveals; Orc; Organization
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
Journal
Nature Communications
Quellenangaben
Volume: 10,
Issue: 1,
Article Number: 3274
Publisher
Nature Publishing Group
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Gene Vector (AGV)
CF Monoclonal Antibodies (CF-MAB)
CF Monoclonal Antibodies (CF-MAB)