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Functional Targeting of DNA Damage to a Nuclear Pore-Associated SUMO-Dependent Ubiquitin Ligase
Shigeki Nagai,1,2*Karine Dubrana,2*Monika Tsai-Pflugfelder,1Marta B. Davidson,3Tania M. Roberts,3Grant W. Brown,3Elisa Varela,1Florence Hediger,2Susan M. Gasser,1,2Nevan J. Krogan4
Recent findings suggest important roles for nuclear organizationin gene expression. In contrast, little is known about how nuclearorganization contributes to genome stability. Epistasis analysis(E-MAP) using DNA repair factors in yeast indicated a functionalrelationship between a nuclear pore subcomplex and Slx5/Slx8,a small ubiquitin-like modifier (SUMO)–dependent ubiquitinligase, which we show physically interact. Real-time imagingand chromatin immunoprecipitation confirmed stable recruitmentof damaged DNA to nuclear pores. Relocation required the Nup84complex and Mec1/Tel1 kinases. Spontaneous gene conversion canbe enhanced in a Slx8- and Nup84-dependent manner by tetheringdonor sites at the nuclear periphery. This suggests that strandbreaks are shunted to nuclear pores for a repair pathway controlledby a conserved SUMO-dependent E3 ligase.
1 Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. 2 Department of Molecular Biology and National Center of Competence in Research Frontiers in Genetics, 30 Quai Ernest Ansermet, 1211 Geneva, Switzerland. 3 Department of Biochemistry, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada. 4 Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, University of California, San Francisco, 1700 Fourth Street, San Francisco, CA 94158, USA.
* These authors contributed equally to this work.
Present address: UMR218, Institut Curie/Section de Recherche,26 Rue d'Ulm, 75231 Paris, and Institut de Radiobiologie Cellulaireet Moléculaire, CEA, 92265 Fontenay aux Roses, France.
To whom correspondence should be addressed. E-mail: susan.gasser{at}fmi.ch
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