title: G-quadruplex-induced instability during leading-strand replication.
abstract: G-quadruplexes are four-stranded nucleic acid structures whose biological functions remain poorly understood. In the yeast S. cerevisiae, we report that G-quadruplexes form and, if not properly processed, pose a specific challenge to replication. We show that the G-quadruplex-prone CEB1 tandem array is tolerated when inserted near ARS305 replication origin in wild-type cells but is very frequently destabilized upon treatment with the potent Phen-DC(3) G-quadruplex ligand, or in the absence of the G-quadruplex-unwinding Pif1 helicase, only when the G-rich strand is the template of leading-strand replication. The orientation-dependent instability is associated with the formation of Rad51-Rad52-dependent X-shaped intermediates during replication detected by two-dimensional (2D) gels, and relies on the presence of intact G-quadruplex motifs in CEB1 and on the activity of ARS305. The asymmetrical behaviour of G-quadruplex prone sequences during replication has implications for their evolutionary dynamics within genomes, including the maintenance of G-rich telomeres.
authors.affiliation: Recombinaison et Instabilité Génétique, Institut Curie Centre de Recherche, CNRS UMR3244, Université Pierre et Marie Curie, Paris Cedex 05, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Lopes
authors.forename: Aurèle
authors.initials: A
authors.lastname: Piazza
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Bermejo
authors.forename: Barry
authors.initials: B
authors.lastname: Kriegsman
authors.forename: Arianna
authors.initials: A
authors.lastname: Colosio
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Teulade-Fichou
authors.forename: Marco
authors.initials: M
authors.lastname: Foiani
authors.forename: Alain
authors.initials: A
authors.lastname: Nicolas
mesh_terms: D002453:Cell Cycle; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D054856:G-Quadruplexes; D023281:Genomics; D008957:Models, Genetic; D009690:Nucleic Acid Conformation; D009713:Nucleotidyltransferases / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D000099270:Y-Family DNA Polymerases
chemical_list: D004265:DNA Helicases; D009713:Nucleotidyltransferases; D051135:Rad51 Recombinase; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; C497197:RAD52 protein, S cerevisiae; C495151:RAD51 protein, S cerevisiae; C100951:REV1 protein, S cerevisiae; D000099270:Y-Family DNA Polymerases; C085463:PIF1 protein, S cerevisiae