title: G4 motifs affect origin positioning and efficiency in two vertebrate replicators.
abstract: DNA replication ensures the accurate duplication of the genome at each cell cycle. It begins at specific sites called replication origins. Genome-wide studies in vertebrates have recently identified a consensus G-rich motif potentially able to form G-quadruplexes (G4) in most replication origins. However, there is no experimental evidence to demonstrate that G4 are actually required for replication initiation. We show here, with two model origins, that G4 motifs are required for replication initiation. Two G4 motifs cooperate in one of our model origins. The other contains only one critical G4, and its orientation determines the precise position of the replication start site. Point mutations affecting the stability of this G4 in vitro also impair origin function. Finally, this G4 is not sufficient for origin activity and must cooperate with a 200-bp cis-regulatory element. In conclusion, our study strongly supports the predicted essential role of G4 in replication initiation.
authors: Institut Jacques Monod, CNRS UMR7592 Université Paris Diderot Equipe Labellisée Ligue contre le cancer, Paris, France.
authors: Anne-Laure
authors: AL
authors: Valton
authors: Vahideh
authors: V
authors: Hassan-Zadeh
authors: Ingrid
authors: I
authors: Lema
authors: Nicole
authors: N
authors: Boggetto
authors: Patrizia
authors: P
authors: Alberti
authors: Carole
authors: C
authors: Saintomé
authors: Jean-Francois
authors: JF
authors: Riou
authors: Marie-Noëlle
authors: MN
authors: Prioleau
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002645:Chickens; D004261:DNA Replication / Q000235:genetics*; D042522:DNA Replication Timing / Q000235:genetics; D054856:G-Quadruplexes; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D059372:Nucleotide Motifs; D017354:Point Mutation; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D018741:Replication Origin / Q000235:genetics*; D024363:Transcription Initiation Site; D014714:Vertebrates / Q000235:genetics*