Department of Genetics, Cell Biology & Development, University of Minnesota Medical School, Minneapolis, MN, USA.
Cell Cycle. 2010 May;9(9):1764-73. doi: 10.4161/cc.9.9.11525. Epub 2010 May 15.
Multi-polar mitosis is strongly linked with aggressive cancers and it is a histological diagnostic of tumor-grade. However, factors that cause chromosomes to segregate to more than two spindle poles are not well understood. Here we show that cohesins Rad21, Smc1 and Smc3 are required for bipolar mitosis in human cells. After Rad21 depletion, chromosomes align at the metaphase plate and bipolar spindles assemble in most cases, but in anaphase the separated chromatids segregate to multiple poles. Time-lapse microscopy revealed that the spindle poles often become split in Rad21-depleted metaphase cells. Interestingly, exogenous expression of non-cleavable Rad21 results in multi-polar anaphase. Since cohesins are present at the spindle poles in mitosis, these data are consistent with a non-chromosomal function of cohesin.
多极有丝分裂与侵袭性癌症密切相关,是肿瘤分级的组织学诊断标准。然而,导致染色体分离到两个以上纺锤极的因素还不太清楚。在这里,我们发现人细胞中的着丝粒蛋白 Rad21、Smc1 和 Smc3 对于两极有丝分裂是必需的。Rad21 耗尽后,染色体在中期板上排列,两极纺锤体在大多数情况下组装,但在后期,分离的染色单体分离到多个极。延时显微镜显示,Rad21 耗尽的中期细胞中的纺锤极经常分裂。有趣的是,非切割 Rad21 的外源表达导致多极后期。由于有丝分裂时着丝粒蛋白位于纺锤极,这些数据与着丝粒蛋白的非染色体功能一致。