Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, Heidelberg D-69117, Germany.
Cell. 2011 Aug 19;146(4):568-81. doi: 10.1016/j.cell.2011.07.031.
Chromosomes must establish stable biorientation prior to anaphase to achieve faithful segregation during cell division. The detailed process by which chromosomes are bioriented and how biorientation is coordinated with spindle assembly and chromosome congression remain unclear. Here, we provide complete 3D kinetochore-tracking datasets throughout cell division by high-resolution imaging of meiosis I in live mouse oocytes. We show that in acentrosomal oocytes, chromosome congression forms an intermediate chromosome configuration, the prometaphase belt, which precedes biorientation. Chromosomes then invade the elongating spindle center to form the metaphase plate and start biorienting. Close to 90% of all chromosomes undergo one or more rounds of error correction of their kinetochore-microtubule attachments before achieving correct biorientation. This process depends on Aurora kinase activity. Our analysis reveals the error-prone nature of homologous chromosome biorientation, providing a possible explanation for the high incidence of aneuploid eggs observed in mammals, including humans.
染色体在有丝分裂后期之前必须建立稳定的双定向，才能在细胞分裂过程中实现忠实的分离。染色体如何双定向，以及双定向如何与纺锤体组装和染色体向心运动协调，这些过程的详细机制仍不清楚。在这里，我们通过对活鼠卵母细胞减数分裂 I 的高分辨率成像，提供了整个细胞分裂过程中完整的三维着丝粒跟踪数据集。我们发现，在无中心体的卵母细胞中，染色体向心运动形成了一个中间染色体构型，即前期带，这先于双定向。然后，染色体侵入延伸的纺锤体中心，形成中期板并开始双定向。在实现正确的双定向之前，几乎 90%的染色体都会经历一轮或多轮的着丝粒-微管连接的错误修正。这个过程依赖于 Aurora 激酶的活性。我们的分析揭示了同源染色体双定向的易错本质，为哺乳动物（包括人类）中观察到的非整倍体卵子发生率高提供了一个可能的解释。
