Fang Lin, Seki Akiko, Fang Guowei
Department of Biological Sciences, Stanford University, Stanford, CA, USA.
Cell Cycle. 2009 Sep 1;8(17):2819-27. doi: 10.4161/cc.8.17.9514. Epub 2009 Sep 13.
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.
纺锤体组装检查点（SAC）通过防止染色体过早分离来控制后期起始，直到每个动粒对的双极微管（MT）附着和动粒间张力完全建立。一旦SAC关闭，泛素连接酶后期促进复合物/细胞周期体的激活会导致securin和细胞周期蛋白B的降解、分离酶的激活以及后期的启动。我们在此报告一个G2期诱导基因SKAP的鉴定和表征，它是后期起始的调节因子。SKAP在有丝分裂中定位于纺锤体微管和动粒。SKAP的缺失不会激活SAC，但会显著延长中期持续时间，延迟分离酶的激活，并降低染色体分离的保真度。我们的研究将SKAP鉴定为中期到后期转变的新型调节因子，并证明分离酶激活的失调会导致染色体分离保真度降低和基因组稳定性降低，且与SAC无关。
