期刊
CELL CYCLE
卷 8, 期 17, 页码 2819-2827出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.8.17.9514
关键词
SKAP; separase; kinetochores; spindle checkpoint; anaphase onset; genomic instability
类别
资金
- Burroughs-Welcome Career Award in Biomedical Research
- National Institutes of Health [GM062852]
The spindle assembly checkpoint ( SAC) controls the anaphase onset by preventing premature chromosome segregation until bipolar microtubule (MT) attachment and inter-kinetochore tension are fully established for every kinetochore pair. Once the SAC is off, activation of the Anaphase-Promoting Complex/Cyclosome, a ubiquitin ligase, leads to the degradation of securin and cyclin B, the activation of separase and the initiation of anaphase. We report here the identification and characterization of a G(2)-induced gene, SKAP, as a regulator for the anaphase onset. SKAP localizes to spindle MTs and kinetochores in mitosis. Depletion of SKAP does not activate the SAC, but substantially increases the duration of metaphase, delays the activation of separase, and decreases the fidelity of chromosome segregation. Our study identifies SKAP as a novel regulator of the metaphase-to-anaphase transition and demonstrates that misregulation of the separase activation results in a reduced fidelity of chromosome segregation and a reduced genomic stability independent of the SAC.
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