Tanaka T, Fuchs J, Loidl J, Nasmyth K
Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, A-1030 Vienna, Austria.
Nat Cell Biol. 2000 Aug;2(8):492-9. doi: 10.1038/35019529.
The multisubunit protein complex cohesin is required to establish cohesion between sister chromatids during S phase and to maintain it during G2 and M phases. Cohesin is essential for mitosis, and even partial defects cause very high rates of chromosome loss. In budding yeast, cohesin associates with specific sites which are distributed along the entire length of a chromosome but are more dense in the vicinity of the centromere. Real-time imaging of individual centromeres tagged with green fluorescent protein suggests that cohesin bound to centromeres is important for bipolar attachment to microtubules. This cohesin is, however, incapable of resisting the consequent force, which leads to sister centromere splitting and chromosome stretching. Meanwhile, cohesin bound to sequences flanking the centromeres prevents sister chromatids from completely unzipping and is required to pull back together sister centromeres that have already split. Cohesin therefore has a central role in generating a dynamic tension between microtubules and sister chromatid cohesion at centromeres, which lasts until chromosome segregation is finally promoted by separin-dependent cleavage of the cohesin subunit Scc1p.
多亚基蛋白复合体黏连蛋白在S期建立姐妹染色单体间的黏连,并在G2期和M期维持这种黏连。黏连蛋白对有丝分裂至关重要,即使是部分缺陷也会导致很高的染色体丢失率。在芽殖酵母中,黏连蛋白与特定位点结合,这些位点沿染色体全长分布,但在着丝粒附近更为密集。对用绿色荧光蛋白标记的单个着丝粒进行实时成像表明,与着丝粒结合的黏连蛋白对双极附着于微管很重要。然而,这种黏连蛋白无法抵抗随之而来的力,这会导致姐妹着丝粒分离和染色体伸展。同时,与着丝粒侧翼序列结合的黏连蛋白可防止姐妹染色单体完全解开,并在姐妹着丝粒已经分离时将它们拉回到一起。因此,黏连蛋白在着丝粒处微管和姐妹染色单体黏连之间产生动态张力方面起着核心作用,这种张力一直持续到黏连蛋白亚基Scc1p依赖于分离酶的切割最终促进染色体分离为止。