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Vol. 18, Issue 8, 2912-2923, August 2007

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Nucleoporins Prevent DNA Damage Accumulation by Modulating Ulp1-dependent Sumoylation Processes

Benoit Palancade^*,, Xianpeng Liu, Maria Garcia-Rubio, Andrès Aguilera, Xiaolan Zhao, and Valérie Doye^*,

*Institut Curie, Centre de Recherche, and Unité Mixte de Recherche 144 Centre National de la Recherche Scientifique, F-75248 Paris, France; Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and Department of Molecular Biology, Centro Andaluz de Biologia Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Cientificas-Universidad de Sevilla, 41092 Sevilla, Spain

Submitted February 14, 2007; Revised May 10, 2007; Accepted May 17, 2007
Monitoring Editor: Karsten Weis

Increasing evidences suggest that nuclear pore complexes (NPCs) control different aspects of nuclear metabolism, including transcription, nuclear organization, and DNA repair. We previously established that the Nup84 complex, a major NPC building block, is part of a genetic network involved in DNA repair. Here, we show that double-strand break (DSB) appearance is linked to a shared function of the Nup84 and the Nup60/Mlp1–2 complexes. Mutants within these complexes exhibit similar genetic interactions and alteration in DNA repair processes as mutants of the SUMO-protease Ulp1. Consistently, these nucleoporins are required for maintenance of proper Ulp1 levels at NPCs and for the establishment of the appropriate sumoylation of several cellular proteins, including the DNA repair factor Yku70. Moreover, restoration of nuclear envelope-associated Ulp1 in nucleoporin mutants reestablishes proper sumoylation patterns and suppresses DSB accumulation and genetic interactions with DNA repair genes. Our results thus provide a molecular mechanism that underlies the connection between NPC and genome stability.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Benoit Palancade (palancad{at}curie.fr).

Abbreviations used: DIC, differential interference contrast; DSB, double-strand break; NHEJ, nonhomologous end joining; HR, homologous recombination; MMS, methyl methane sulfonate; NPC, nuclear pore complex; SD, standard deviation; SSA, single strand annealing; wt, wild type.

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