PDF(Pubmed)
Abstract：
Centromeres are scaffolds for the assembly of kinetochores that ensure chromosome segregation during cell division. How vertebrate centromeres obtain a three-dimensional structure to accomplish their primary function is unclear. Using super-resolution imaging, capture-C, and polymer modeling, we show that vertebrate centromeres are partitioned by condensins into two subdomains during mitosis. The bipartite structure is found in human, mouse, and chicken cells and is therefore a fundamental feature of vertebrate centromeres. Super-resolution imaging and electron tomography reveal that bipartite centromeres assemble bipartite kinetochores, with each subdomain binding a distinct microtubule bundle. Cohesin links the centromere subdomains, limiting their separation in response to spindle forces and avoiding merotelic kinetochore-spindle attachments. Lagging chromosomes during cancer cell divisions frequently have merotelic attachments in which the centromere subdomains are separated and bioriented. Our work reveals a fundamental aspect of vertebrate centromere biology with implications for understanding the mechanisms that guarantee faithful chromosome segregation.
摘要：
着丝粒是用于组装动子的支架，可确保细胞分裂过程中的染色体分离。脊椎动物着丝粒如何获得三维结构以实现其主要功能尚不清楚。使用超分辨率成像，capture-C,和聚合物建模，我们显示脊椎动物着丝粒在有丝分裂过程中被凝集素划分为两个亚结构域。二分结构在人类中发现，鼠标,和鸡细胞，因此是脊椎动物着丝粒的基本特征。超分辨率成像和电子层析成像显示，二分着丝粒组装二分动体，每个子域结合一个不同的微管束。Cohesin连接着丝粒子域，限制它们的分离，以响应主轴力，并避免使用merotelic动子-主轴附件。癌细胞分裂过程中的滞后染色体通常具有微晶体附着，其中着丝粒亚结构域被分离并双向定位。我们的工作揭示了脊椎动物着丝粒生物学的一个基本方面，对理解保证忠实染色体分离的机制具有重要意义。
