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

被引：351

作者：

Nagai, Shigeki ^{[1
,2
,3
]}

Dubrana, Karine ^{[2
,3
]}

Tsai-Pflugfelder, Monika ^{[1
]}

Davidson, Marta B. ^{[4
]}

Roberts, Tania M. ^{[4
]}

Brown, Grant W. ^{[4
]}

Varela, Elisa ^{[1
]}

Hediger, Florence ^{[2
,3
]}

Gasser, Susan M. ^{[1
,2
,3
]}

Krogan, Nevan J. ^{[5
]}

机构：

[1] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland

[2] Univ Geneva, Dept Mol Biol, CH-1211 Geneva, Switzerland

[3] Natl Ctr Competence Res Frontiers Genet, CH-1211 Geneva, Switzerland

[4] Univ Toronto, Dept Biochem, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada

[5] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, Calif Inst Quantitat Biomed Res, San Francisco, CA 94158 USA

来源：

SCIENCE | 2008年 / 322卷 / 5901期

基金：

瑞士国家科学基金会;

关键词：

D O I：

10.1126/science.1162790

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

收藏

页码：597 / 602

页数：6

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