Palancade Benoit, Liu Xianpeng, Garcia-Rubio Maria, Aguilera Andrès, Zhao Xiaolan, Doye Valérie
Institut Curie, Centre de Recherche, and Unité Mixte de Recherche 144 Centre National de la Recherche Scientifique, F-75248 Paris, France.
Mol Biol Cell. 2007 Aug;18(8):2912-23. doi: 10.1091/mbc.e07-02-0123. Epub 2007 May 30.
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.
越来越多的证据表明，核孔复合体（NPC）控制着核代谢的不同方面，包括转录、核组织和DNA修复。我们之前证实，作为NPC主要组成部分的Nup84复合体是参与DNA修复的遗传网络的一部分。在此，我们表明双链断裂（DSB）的出现与Nup84和Nup60/Mlp1 - 2复合体的共同功能相关。这些复合体内的突变体表现出与SUMO蛋白酶Ulp1突变体相似的遗传相互作用以及DNA修复过程的改变。一致的是，这些核孔蛋白对于在NPC处维持适当的Ulp1水平以及建立包括DNA修复因子Yku70在内的几种细胞蛋白的适当SUMO化是必需的。此外，在核孔蛋白突变体中恢复核膜相关的Ulp1可重新建立适当的SUMO化模式，并抑制DSB积累以及与DNA修复基因的遗传相互作用。因此，我们的结果提供了一种分子机制，该机制构成了NPC与基因组稳定性之间联系的基础。
