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Published 16 January 2006. doi:10.1083/jcb.200505159
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 2, 189-199
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Article

 Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region

Pierre Therizols1, Cécile Fairhead1, Ghislain G. Cabal2, Auguste Genovesio3, Jean-Christophe Olivo-Marin3, Bernard Dujon1, and Emmanuelle Fabre1

1 Unité 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
2 Unité de Biologie Cellulaire du Noyau, Département Biologie Cellulaire et Infection, Institut Pasteur, 75724 Paris Cedex, France
3 Unité d'Analyse d'Images Quantitative, Département Biologie Cellulaire et Infection, Institut Pasteur, 75724 Paris Cedex, France

Correspondence to Corresponding author: efabre{at}pasteur.fr

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.

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.


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