Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase. Science (New York, N.Y.) [Science] Journal article

Title	Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase.
Author(s)	Nagai S, Dubrana K, Tsai-Pflugfelder M, Davidson MB, Roberts TM, Brown GW, Varela E, Hediger F, Gasser SM, Krogan NJ
Institution	Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Source	Science 2008 Oct 24; 322(5901):597-602.
MeSH	Chromatin Immunoprecipitation DNA Breaks, Double-Stranded DNA Repair DNA, Fungal DNA-Binding Proteins Deoxyribonucleases, Type II Site-Specific Gene Conversion Genes, Fungal Immunoprecipitation Intracellular Signaling Peptides and Proteins Kinetics Nuclear Pore Nuclear Pore Complex Proteins Protein-Serine-Threonine Kinases Recombination, Genetic Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Small Ubiquitin-Related Modifier Proteins Ubiquitin-Protein Ligases Zinc Fingers
Abstract	Recent findings suggest important roles for nuclear organization in gene expression. In contrast, little is known about how nuclear organization contributes to genome stability. Epistasis analysis (E-MAP) using DNA repair factors in yeast indicated a functional relationship between a nuclear pore subcomplex and Slx5/Slx8, a small ubiquitin-like modifier (SUMO)-dependent ubiquitin ligase, which we show physically interact. Real-time imaging and chromatin immunoprecipitation confirmed stable recruitment of damaged DNA to nuclear pores. Relocation required the Nup84 complex and Mec1/Tel1 kinases. Spontaneous gene conversion can be enhanced in a Slx8- and Nup84-dependent manner by tethering donor sites at the nuclear periphery. This suggests that strand breaks are shunted to nuclear pores for a repair pathway controlled by a conserved SUMO-dependent E3 ligase.
Language	eng
Pub Type(s)	Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
PubMed ID	18948542

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