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

• DOI: 10.1091/mbc.e07-02-0123
• Publication Date: 2007-05-31T01:10:44Z
• Authors: Benoit Palancade; Xianpeng Liu; Maria Garcia-Rubio; Andrès Aguilera; Xiaolan Zhao; Valérie Doye
• Keywords: Saccharomyces cerevisiae Proteins; DNA Repair; Nuclear Envelope; DNA repair; Saccharomyces cerevisiae; Karyopherins; 03 medical and health sciences; Nuclear Pore Complex Proteins/metabolism; Small Ubiquitin-Related Modifier Proteins/metabolism; Enzyme Stability; DNA Breaks, Double-Stranded; Cysteine Endopeptidases/metabolism; Sumoylation processes; 0303 health sciences; Nuclear Proteins; RNA-Binding Proteins; 3. Good health; Nuclear Pore Complex Proteins; Nuclear Pore Complexes (NPCs); Cysteine Endopeptidases; Protein Transport; Phenotype; Mutation; Small Ubiquitin-Related Modifier Proteins; Nuclear metabolism; Saccharomyces cerevisiae/enzymology; DNA Damage

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.