Fu Guosheng, Hua Shasha, Ward Tarsha, Ding Xia, Yang Yong, Guo Zhen, Yao Xuebiao
Laboratory of Cellular Dynamics, University of Science & Technology of China, Hefei National Laboratory, Hefei 230027, China.
Biochem Biophys Res Commun. 2007 Jun 8;357(3):672-8. doi: 10.1016/j.bbrc.2007.03.204. Epub 2007 Apr 12.
Chromosome segregation and proper alignment in mitosis relies on cohesion between sister chromatids and the interaction of the kinetochore with spindle microtubules. Vertebrate Sgo 1 localizes to kinetochores and is required to prevent premature sister centromere separation in mitosis. Sgo 1 is degraded by the anaphase-promoting complex, allowing the separation of sister centromeres in anaphase. However, little is known about the molecular basis of Sgo 1 degradation and its temporal control during mitosis. Here, we show that APC/C targets human Sgo 1 for degradation through a destruction box motif (D-box) in its C-terminus. Mutation in the D-box causes transient metaphase arrest, and mutation in the D-box leads to defects in chromosome alignment and segregation through its effect on the localization of Aurora B and CENP-E. These results provide a link between sister centromere cohesion and bipolar attachment of kinetochores.
有丝分裂过程中的染色体分离和正确排列依赖于姐妹染色单体之间的黏连以及动粒与纺锤体微管的相互作用。脊椎动物的Sgo 1定位于动粒，是防止有丝分裂过程中姐妹着丝粒过早分离所必需的。Sgo 1在后期促进复合物的作用下被降解，从而允许后期姐妹着丝粒分离。然而，关于Sgo 1降解的分子基础及其在有丝分裂过程中的时间控制知之甚少。在这里，我们表明后期促进复合物/细胞周期蛋白复合体（APC/C）通过人Sgo 1 C端的一个破坏框基序（D-box）靶向其进行降解。D-box中的突变会导致短暂的中期停滞，并且D-box中的突变会通过影响极光激酶B（Aurora B）和着丝粒蛋白E（CENP-E）的定位而导致染色体排列和分离缺陷。这些结果提供了姐妹着丝粒黏连与动粒双极附着之间的联系。
