Involvement of G-quadruplex Regions in Mammalian Replication Origin Activity

Nat Commun. 2019 Jul 22;10(1):3274. doi: 10.1038/s41467-019-11104-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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