期刊
ACS CHEMICAL BIOLOGY
卷 11, 期 6, 页码 1544-1551出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.6b00203
关键词
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资金
- State Baden-Wurttemberg
- National Insitutes of Health [R35CA197589, GM39565]
- Konstanz Research School Chemical Biology (KoRS-CB)
- [SFB 969]
The genetic integrity of each organism is intimately tied to. the correct segregation of its genome-during mitosis. Insights into the underlying mechanisms are fundamental for both basic research and the development of novel strategies to treat mitosis-televant diseases such as cancer. Due to their fast mode of action, small molecules are invaluable tools to dissect mitosis. Yet, there is a great demand for novel antimitotic compounds. We performed a chemical genetic suppression screen to identify compounds that restore spindle bipolarity in cells treated with Monastrol, an inhibitor of the mitotic kinesin Eg5. We identified one compound MAC1 that rescued spindle bipolarity in cells lacking Eg5 activity. Mechanistically, MAC1 induces the formation of additional microtubule nucleation centers, which allows kinesin Kif15-dependent bipolar spindle assembly in the absence of Eg5 activity. Thus, our chemical genetic suppression screen revealed novel unexpected insights into the mechanism of spindle assembly in mammalian cells.
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