title: The DNA damage response at eroded telomeres and tethering to the nuclear pore complex.
abstract: The ends of linear eukaryotic chromosomes are protected by telomeres, which serve to ensure proper chromosome replication and to prevent spurious recombination at chromosome ends. In this study, we show by single cell analysis that in the absence of telomerase, a single short telomere is sufficient to induce the recruitment of checkpoint and recombination proteins. Notably, a DNA damage response at eroded telomeres starts many generations before senescence and is characterized by the recruitment of Cdc13 (cell division cycle 13), replication protein A, DNA damage checkpoint proteins and the DNA repair protein Rad52 into a single focus. Moreover, we show that eroded telomeres, although remaining at the nuclear periphery, move to the nuclear pore complex. Our results link the DNA damage response at eroded telomeres to changes in subnuclear localization and suggest the existence of collapsed replication forks at eroded telomeres.
authors: CNRS, Unité Propre de Recherche 3081, Genome Instability and Carcinogenesis Conventionné par l'Université d'Aix-Marseille 2, 13402 Marseille Cedex 20, France.
authors: Basheer
authors: B
authors: Khadaroo
authors: M Teresa
authors: MT
authors: Teixeira
authors: Pierre
authors: P
authors: Luciano
authors: Nadine
authors: N
authors: Eckert-Boulet
authors: Susanne M
authors: SM
authors: Germann
authors: Marie Noelle
authors: MN
authors: Simon
authors: Irene
authors: I
authors: Gallina
authors: Pauline
authors: P
authors: Abdallah
authors: Eric
authors: E
authors: Gilson
authors: Vincent
authors: V
authors: Géli
authors: Michael
authors: M
authors: Lisby
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000235:genetics; D016195:G2 Phase; D006238:Haploidy; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D051716:Replication Protein A / Q000235:genetics / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C452219:Cdc13 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004277:DNA, Single-Stranded; C440014:LCD1 protein, S cerevisiae; D008164:Luminescent Proteins; C091271:NUP133 protein, S cerevisiae; C077727:NUP49 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D011993:Recombinant Fusion Proteins; D051716:Replication Protein A; D029701:Saccharomyces cerevisiae Proteins; D034501:Telomere-Binding Proteins; C509185:EST2 protein, S cerevisiae; D019098:Telomerase