Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase

Shigeki Nagai, Karine Dubrana, Monika Tsai-Pflugfelder, Marta B. Davidson, Tania M. Roberts, Grant W. Brown, Elisa Varela, Florence Hediger, Susan M. Gasser, Nevan J. Krogan

Research output: Contribution to journalArticlepeer-review

364 Scopus citations

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.

Original languageEnglish
Pages (from-to)597-602
Number of pages6
JournalScience
Volume322
Issue number5901
DOIs
StatePublished - 24 Oct 2008
Externally publishedYes

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