Department of Biology, 2 Department of Mathematics, and 3 Department Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
J Cell Biol. 2013 Nov 11;203(3):407-16. doi: 10.1083/jcb.201307104. Epub 2013 Nov 4.
The mitotic segregation apparatus composed of microtubules and chromatin functions to faithfully partition a duplicated genome into two daughter cells. Microtubules exert extensional pulling force on sister chromatids toward opposite poles, whereas pericentric chromatin resists with contractile springlike properties. Tension generated from these opposing forces silences the spindle checkpoint to ensure accurate chromosome segregation. It is unknown how the cell senses tension across multiple microtubule attachment sites, considering the stochastic dynamics of microtubule growth and shortening. In budding yeast, there is one microtubule attachment site per chromosome. By labeling several chromosomes, we find that pericentromeres display coordinated motion and stretching in metaphase. The pericentromeres of different chromosomes exhibit physical linkage dependent on centromere function and structural maintenance of chromosomes complexes. Coordinated motion is dependent on condensin and the kinesin motor Cin8, whereas coordinated stretching is dependent on pericentric cohesin and Cin8. Linking of pericentric chromatin through cohesin, condensin, and kinetochore microtubules functions to coordinate dynamics across multiple attachment sites.
由微管和染色质组成的有丝分裂分离装置将复制的基因组忠实地分配到两个子细胞中。微管对姐妹染色单体施加向外的拉伸力，使其朝向相反的两极移动，而着丝粒周围的染色质则具有收缩的弹性特性。这些相反的力产生的张力使纺锤体检查点沉默，以确保染色体的准确分离。由于微管生长和缩短的随机性，目前尚不清楚细胞如何感知多个微管附着位点的张力。在芽殖酵母中，每个染色体只有一个微管附着位点。通过标记几个染色体，我们发现着丝粒在中期表现出协调的运动和拉伸。不同染色体的着丝粒表现出物理连接，这取决于着丝粒的功能和染色体结构维持复合物。协调运动依赖于凝聚素和驱动蛋白 Cin8，而协调拉伸则依赖于着丝粒周围的黏合蛋白和 Cin8。通过黏合蛋白、凝聚素和动粒微管将着丝粒周围的染色质连接起来，可起到协调多个附着位点动力学的作用。
