title: Elucidation of the DNA end-replication problem in Saccharomyces cerevisiae.
abstract: The model for telomere shortening at each replication cycle is currently incomplete, and the exact contribution of the telomeric 3' overhang to the shortening rate remains unclear. Here, we demonstrate key steps of the mechanism of telomere replication in Saccharomyces cerevisiae. By following the dynamics of telomeres during replication at near-nucleotide resolution, we find that the leading-strand synthesis generates blunt-end intermediates before being 5'-resected and filled in. Importantly, the shortening rate is set by positioning the last Okazaki fragments at the very ends of the chromosome. Thus, telomeres shorten in direct proportion to the 3' overhang lengths of 5-10 nucleotides that are present in parental templates. Furthermore, the telomeric protein Cdc13 coordinates leading- and lagging-strand syntheses. Taken together, our data unravel a precise choreography of telomere replication elucidating the DNA end-replication problem and provide a framework to understand the control of the cell proliferation potential.
authors.affiliation: Centre National de la Recherche Scientifique, UMR8226, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, 75005 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR8226, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, 75005 Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Soudet
authors.affiliation: Centre National de la Recherche Scientifique, UMR8226, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, 75005 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR8226, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, 75005 Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Jolivet
authors.affiliation: Centre National de la Recherche Scientifique, UMR8226, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, 75005 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR8226, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, 75005 Paris, France. Electronic address: teresa.teixeira@ibpc.fr.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Teixeira
mesh_terms: D049109:Cell Proliferation; D015825:Chromosomes, Fungal; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004261:DNA Replication; D004277:DNA, Single-Stranded; D015966:Gene Expression Regulation, Fungal; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000737:chemistry*; D059505:Telomere Homeostasis; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C452219:Cdc13 protein, S cerevisiae; D004277:DNA, Single-Stranded; C022262:Okazaki fragments; D029701:Saccharomyces cerevisiae Proteins; D034501:Telomere-Binding Proteins; D004247:DNA