In the yeast Saccharomyces cerevisiae that lacks lamins, the nuclear pore complex (NPC) has been proposed to serve a role in chromatin organization. Here, using fluorescence microscopy in living cells, we show that nuclear pore proteins of the Nup84 core complex, Nup84p, Nup145Cp, Nup120p, and Nup133p, serve to anchor telomere XI-L at the nuclear periphery. The integrity of this complex is shown to be required for repression of a URA3 gene inserted in the subtelomeric region of this chromosome end. Furthermore, altering the integrity of this complex decreases the efficiency of repair of a DNA double-strand break (DSB) only when it is generated in the subtelomeric region, even though the repair machinery is functional. These effects are specific to the Nup84 complex. Our observations thus confirm and extend the role played by the NPC, through the Nup84 complex, in the functional organization of chromatin. They also indicate that anchoring of telomeres is essential for efficient repair of DSBs occurring therein and is important for preserving genome integrity.
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16 January 2006
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January 17 2006
Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region
Pierre Therizols,
Pierre Therizols
1Unité de Génétique Moléculaire des Levures (URA 2171 Centre National de la Recherche Scientifique, UFR 927 Université Pierre et Marie Curie), Département Structure et Dynamique des Génomes, Institut Pasteur, 75724 Paris Cedex, France
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Cécile Fairhead,
Cécile Fairhead
1Unité de Génétique Moléculaire des Levures (URA 2171 Centre National de la Recherche Scientifique, UFR 927 Université Pierre et Marie Curie), Département Structure et Dynamique des Génomes, Institut Pasteur, 75724 Paris Cedex, France
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Ghislain G. Cabal,
Ghislain G. Cabal
2Unité de Biologie Cellulaire du Noyau, Département Biologie Cellulaire et Infection, Institut Pasteur, 75724 Paris Cedex, France
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Auguste Genovesio,
Auguste Genovesio
3Unité d'Analyse d'Images Quantitative, Département Biologie Cellulaire et Infection, Institut Pasteur, 75724 Paris Cedex, France
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Jean-Christophe Olivo-Marin,
Jean-Christophe Olivo-Marin
3Unité d'Analyse d'Images Quantitative, Département Biologie Cellulaire et Infection, Institut Pasteur, 75724 Paris Cedex, France
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Bernard Dujon,
Bernard Dujon
1Unité de Génétique Moléculaire des Levures (URA 2171 Centre National de la Recherche Scientifique, UFR 927 Université Pierre et Marie Curie), Département Structure et Dynamique des Génomes, Institut Pasteur, 75724 Paris Cedex, France
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Emmanuelle Fabre
Emmanuelle Fabre
1Unité de Génétique Moléculaire des Levures (URA 2171 Centre National de la Recherche Scientifique, UFR 927 Université Pierre et Marie Curie), Département Structure et Dynamique des Génomes, Institut Pasteur, 75724 Paris Cedex, France
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Pierre Therizols
1Unité de Génétique Moléculaire des Levures (URA 2171 Centre National de la Recherche Scientifique, UFR 927 Université Pierre et Marie Curie), Département Structure et Dynamique des Génomes, Institut Pasteur, 75724 Paris Cedex, France
Cécile Fairhead
1Unité de Génétique Moléculaire des Levures (URA 2171 Centre National de la Recherche Scientifique, UFR 927 Université Pierre et Marie Curie), Département Structure et Dynamique des Génomes, Institut Pasteur, 75724 Paris Cedex, France
Ghislain G. Cabal
2Unité de Biologie Cellulaire du Noyau, Département Biologie Cellulaire et Infection, Institut Pasteur, 75724 Paris Cedex, France
Auguste Genovesio
3Unité d'Analyse d'Images Quantitative, Département Biologie Cellulaire et Infection, Institut Pasteur, 75724 Paris Cedex, France
Jean-Christophe Olivo-Marin
3Unité d'Analyse d'Images Quantitative, Département Biologie Cellulaire et Infection, Institut Pasteur, 75724 Paris Cedex, France
Bernard Dujon
1Unité de Génétique Moléculaire des Levures (URA 2171 Centre National de la Recherche Scientifique, UFR 927 Université Pierre et Marie Curie), Département Structure et Dynamique des Génomes, Institut Pasteur, 75724 Paris Cedex, France
Emmanuelle Fabre
1Unité de Génétique Moléculaire des Levures (URA 2171 Centre National de la Recherche Scientifique, UFR 927 Université Pierre et Marie Curie), Département Structure et Dynamique des Génomes, Institut Pasteur, 75724 Paris Cedex, France
Correspondence to Corresponding author: [email protected]
Abbreviations used in this paper: 3D, three-dimensional; DSB, double-strand break; GC, gene conversion; HR, homologous recombination; NHEJ, nonhomologous end joining; NPC, nuclear pore complex; TPE, telomere position effect; 5-FOA, 5-fluoro-orotic acid.
Received:
May 25 2005
Accepted:
December 14 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2006
J Cell Biol (2006) 172 (2): 189–199.
Article history
Received:
May 25 2005
Accepted:
December 14 2005
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Repair at the nuclear periphery
Citation
Pierre Therizols, Cécile Fairhead, Ghislain G. Cabal, Auguste Genovesio, Jean-Christophe Olivo-Marin, Bernard Dujon, Emmanuelle Fabre; Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region . J Cell Biol 16 January 2006; 172 (2): 189–199. doi: https://doi.org/10.1083/jcb.200505159
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