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PMID: 17538013 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Nucleoporins prevent DNA damage accumulation by modulating Ulp1-dependent sumoylation processes.

Molecular biology of the cell ·Vol. 18 ·No. 8 ·2007-08-00 ·Pages 2912-23

Palancade B, Liu X, Garcia-Rubio M, Aguilera A, Zhao X, Doye V

Abstract

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.

MeSH Terms
Cysteine Endopeptidases/metabolism DNA Breaks, Double-Stranded DNA Damage DNA Repair Enzyme Stability Karyopherins/metabolism Mutation/genetics Nuclear Envelope/metabolism Nuclear Pore Complex Proteins/metabolism Nuclear Proteins/metabolism Phenotype Protein Transport RNA-Binding Proteins Saccharomyces cerevisiae/cytology,enzymology Saccharomyces cerevisiae Proteins/metabolism Small Ubiquitin-Related Modifier Proteins/metabolism
Chemicals
Karyopherins MLP1 protein, S cerevisiae Nuclear Pore Complex Proteins Nuclear Proteins RNA-Binding Proteins Saccharomyces cerevisiae Proteins Small Ubiquitin-Related Modifier Proteins Cysteine Endopeptidases Ulp1 protease
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Palancade Benoit
Institut Curie, Centre de Recherche, and Unité Mixte de Recherche 144 Centre National de la Recherche Scientifique, F-75248 Paris, France. [email protected]
Liu Xianpeng
Garcia-Rubio Maria
Aguilera Andrès
Zhao Xiaolan
Doye Valérie
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e07-02-0123
Email
[email protected]
Published
2007-08-00
Epub
2007-00-30
Pages
2912-23
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC1949349
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e07-02-0123 PMC Full Text View journal details
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