The DNA damage response at eroded telomeres and tethering to the nuclear pore complex

Basheer Khadaroo; M Teresa Teixeira; Pierre Luciano; Nadine Eckert-Boulet; Susanne M Germann; Marie Noelle Simon; Irene Gallina; Pauline Abdallah; Eric Gilson; Vincent Géli; Michael Lisby

doi:10.1038/ncb1910

The DNA damage response at eroded telomeres and tethering to the nuclear pore complex

Basheer Khadaroo, M Teresa Teixeira, Pierre Luciano, Nadine Eckert-Boulet, Susanne M Germann, Marie Noelle Simon, Irene Gallina, Pauline Abdallah, Eric Gilson, Vincent Géli, Michael Lisby

Functional Genomics

136 Citations (Scopus)

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.

Original language	English
Journal	Nature Cell Biology
Volume	11
Issue number	8
Pages (from-to)	980-7
Number of pages	7
ISSN	1465-7392
DOIs	https://doi.org/10.1038/ncb1910
Publication status	Published - 2009

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@article{13733630f3a311deba73000ea68e967b,

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.",

author = "Basheer Khadaroo and Teixeira, {M Teresa} and Pierre Luciano and Nadine Eckert-Boulet and Germann, {Susanne M} and Simon, {Marie Noelle} and Irene Gallina and Pauline Abdallah and Eric Gilson and Vincent G{\'e}li and Michael Lisby",

note = "Keywords: Adaptor Proteins, Signal Transducing; Cell Cycle Proteins; Chromatin Immunoprecipitation; DNA Damage; DNA Repair; DNA, Single-Stranded; G2 Phase; Haploidy; Luminescent Proteins; Microscopy, Fluorescence; Mutation; Nuclear Pore; Nuclear Pore Complex Proteins; Rad52 DNA Repair and Recombination Protein; Recombinant Fusion Proteins; Replication Protein A; S Phase; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Telomerase; Telomere; Telomere-Binding Proteins",

year = "2009",

doi = "10.1038/ncb1910",

language = "English",

volume = "11",

pages = "980--7",

journal = "Nature Cell Biology",

issn = "1465-7392",

publisher = "nature publishing group",

number = "8",

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TY - JOUR

T1 - The DNA damage response at eroded telomeres and tethering to the nuclear pore complex

AU - Khadaroo, Basheer

AU - Teixeira, M Teresa

AU - Luciano, Pierre

AU - Eckert-Boulet, Nadine

AU - Germann, Susanne M

AU - Simon, Marie Noelle

AU - Gallina, Irene

AU - Abdallah, Pauline

AU - Gilson, Eric

AU - Géli, Vincent

AU - Lisby, Michael

N1 - Keywords: Adaptor Proteins, Signal Transducing; Cell Cycle Proteins; Chromatin Immunoprecipitation; DNA Damage; DNA Repair; DNA, Single-Stranded; G2 Phase; Haploidy; Luminescent Proteins; Microscopy, Fluorescence; Mutation; Nuclear Pore; Nuclear Pore Complex Proteins; Rad52 DNA Repair and Recombination Protein; Recombinant Fusion Proteins; Replication Protein A; S Phase; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Telomerase; Telomere; Telomere-Binding Proteins

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1038/ncb1910

DO - 10.1038/ncb1910

M3 - Journal article

C2 - 19597487

SN - 1465-7392

VL - 11

SP - 980

EP - 987

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 8

ER -

The DNA damage response at eroded telomeres and tethering to the nuclear pore complex

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