Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region.
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.
Therizols
Pierre
P
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.
Fairhead
Cécile
C
Cabal
Ghislain G
GG
Genovesio
Auguste
A
Olivo-Marin
Jean-Christophe
JC
Dujon
Bernard
B
Fabre
Emmanuelle
E
D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D015825:Chromosomes, Fungal; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D020868:Gene Silencing; D008969:Molecular Sequence Data; D022022:Nuclear Pore / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*
C495981:Esc1 protein, S cerevisiae; C097894:NUP84 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA