The DNA damage response at eroded telomeres and tethering to the nuclear pore complex.
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.
Khadaroo
Basheer
B
CNRS, Unité Propre de Recherche 3081, Genome Instability and Carcinogenesis Conventionné par l'Université d'Aix-Marseille 2, 13402 Marseille Cedex 20, France.
Teixeira
M Teresa
MT
Luciano
Pierre
P
Eckert-Boulet
Nadine
N
Germann
Susanne M
SM
Simon
Marie Noelle
MN
Gallina
Irene
I
Abdallah
Pauline
P
Gilson
Eric
E
Géli
Vincent
V
Lisby
Michael
M
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
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