荷兰乌得勒支大学Geert J.P.L. Kops等研究人员合作发现，有丝分裂中的脊椎动物中心粒在功能上是由黏连蛋白稳定的两部分结构。相关论文于2024年5月13日在线发表于国际学术期刊《细胞》。
通过超分辨率成像、capture-C和聚合物建模，研究人员发现脊椎动物的中心粒在有丝分裂过程中被condensin分成两个亚域。人、小鼠和鸡的细胞中都存在这种双分区结构，因此这是脊椎动物中心粒的一个基本特征。超分辨率成像和电子断层扫描显示，两部分中心粒组装了两部分动点，每个亚域结合一个不同的微管束。
黏连蛋白将中心粒亚域连接起来，限制它们在主轴力作用下分离，并避免动点核心与主轴连接。在癌细胞分裂过程中，滞后的染色体经常出现merotelic附着，在这种情况下，中心粒亚域被分离和双向化。该研究揭示了脊椎动物中心粒生物学的一个基本方面，对理解保证染色体忠实分离的机制具有重要意义。
据介绍，中心粒是着丝点组装的支架，可确保细胞分裂过程中染色体的分离。脊椎动物的中心粒如何获得三维结构以实现其主要功能尚不清楚。
附：英文原文
Title: Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin
Author: Carlos Sacristan, Kumiko Samejima, Lorena Andrade Ruiz, Moonmoon Deb, Maaike L.A. Lambers, Adam Buckle, Chris A. Brackley, Daniel Robertson, Tetsuya Hori, Shaun Webb, Robert Kiewisz, Tristan Bepler, Elose van Kwawegen, Patrik Risteski, Kruno Vukui, Iva M. Toli, Thomas Müller-Reichert, Tatsuo Fukagawa, Nick Gilbert, Davide Marenduzzo, William C. Earnshaw, Geert J.P.L. Kops
Issue&Volume: 2024-05-13
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.
DOI: 10.1016/j.cell.2024.04.014
Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00409-4