期刊
SCIENCE
卷 322, 期 5901, 页码 597-602出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1162790
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资金
- Novartis Research Foundation
- Swiss Cancer League
- Swiss National Science Foundation
- Sandler Family Foundation
- NIH
- National Cancer Institute of Canada
- Canadian Cancer Society
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.
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