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GENES & DEVELOPMENT 22:1153-1158, 2008
©2008 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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RESEARCH COMMUNICATION

Multiple pathways inhibit NHEJ at telomeres

Stéphane Marcand1,5, Benjamin Pardo1,3, Ariane Gratias1,4, Sabrina Cahun1, and Isabelle Callebaut2

1 Centre National de la Recherche Scientifque (CNRS) UMR 217, Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), CEA/Fontenay, 92265 Fontenay-aux-roses cedex, France; 2 CNRS UMR 7590, Universités Paris 6 et Paris 7, 75015 Paris, France

The nonhomologous end-joining (NHEJ) repair pathway is inhibited at telomeres, preventing chromosome fusion. In budding yeast Saccharomyces cerevisiae, the Rap1 protein directly binds the telomere sequences and is required for NHEJ inhibition. Here we show that the Rap1 C-terminal domain establishes two parallel inhibitory pathways through the proteins Rif2 and Sir4. In addition, the central domain of Rap1 inhibits NHEJ independently of Rif2 and Sir4. Thus, Rap1 establishes several independent pathways to prevent telomere fusions. We discuss a possible mechanism that would explain Rif2 multifunctionality at telomeres and the recent evolutionary origin of Rif2 from an origin recognition complex (ORC) subunit.

[Keywords: Genome stability; NHEJ; Rap1; Rif2; Sir4; telomere]]

Received August 30, 2007; revised version accepted February 29, 2008.


3 Present addresses: Department of Molecular Biology, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Avenida America Vespucio S/N, 41092 Sevilla, Spain;

4 Université Paris 11, IBP, Bat 630, 91160 Orsay, France.

5 Corresponding author:

E-MAIL stephane.marcand{at}cea.fr; FAX 33-1-46549180.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.455108.


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