Tang Zhanyun, Sun Yuxiao, Harley Sara E, Zou Hui, Yu Hongtao
Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9041, USA.
Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18012-7. doi: 10.1073/pnas.0408600102. Epub 2004 Dec 16.
Sister chromatids in mammalian cells remain attached mostly at their centromeres at metaphase because of the loss of cohesion along chromosome arms in prophase. Here, we report that Bub1 retains centromeric cohesion in mitosis of human cells. Depletion of Bub1 or Shugoshin (Sgo1) in HeLa cells by RNA interference causes massive missegregation of sister chromatids that originates at centromeres. Surprisingly, loss of chromatid cohesion in Bub1 and Sgo1 RNA-interference cells does not appear to require the full activation of separase but, instead, triggers a mitotic arrest that depends on Mad2 and Aurora B. Bub1 maintains the steady-state levels and centromeric localization of Sgo1. Therefore, Bub1 protects centromeric cohesion through Shugoshin in mitosis.
由于前期染色体臂上黏连蛋白的缺失，哺乳动物细胞中的姐妹染色单体在中期时大多在着丝粒处相连。在此，我们报告Bub1在人类细胞有丝分裂过程中维持着丝粒处的黏连。通过RNA干扰使HeLa细胞中的Bub1或守护蛋白（Sgo1）缺失，会导致姐妹染色单体大量错分离，这种错分离起源于着丝粒。令人惊讶的是，Bub1和Sgo1 RNA干扰细胞中染色单体黏连的丧失似乎并不需要分离酶的完全激活，相反，会触发依赖于Mad2和极光激酶B的有丝分裂停滞。Bub1维持Sgo1的稳态水平及其着丝粒定位。因此，Bub1在有丝分裂过程中通过守护蛋白保护着丝粒处的黏连。
