Nucleoporins prevent DNA damage accumulation by modulating Ulp1-dependent sumoylation processes.
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.
Palancade
Benoit
B
Institut Curie, Centre de Recherche, and Unité Mixte de Recherche 144 Centre National de la Recherche Scientifique, F-75248 Paris, France. palancad@crie.fr
Liu
Xianpeng
X
Garcia-Rubio
Maria
M
Aguilera
Andrès
A
Zhao
Xiaolan
X
Doye
Valérie
V
D003546:Cysteine Endopeptidases / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004795:Enzyme Stability; D028884:Karyopherins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009685:Nuclear Envelope / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D021381:Protein Transport; D016601:RNA-Binding Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*
D028884:Karyopherins; C080988:MLP1 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D003546:Cysteine Endopeptidases; C118083:Ulp1 protease