Department of Biochemistry and Department of Urology, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
J Cell Biol. 2014 Jun 23;205(6):781-90. doi: 10.1083/jcb.201308172. Epub 2014 Jun 16.
During mitosis, genomic DNA is condensed into chromosomes to promote its equal segregation into daughter cells. Chromosome condensation occurs during cell cycle progression from G2 phase to mitosis. Failure of chromosome compaction at prophase leads to subsequent misregulation of chromosomes. However, the molecular mechanism that controls the early phase of mitotic chromosome condensation is largely unknown. Here, we show that Mps1 regulates initial chromosome condensation during mitosis. We identify condensin II as a novel Mps1-associated protein. Mps1 phosphorylates one of the condensin II subunits, CAP-H2, at Ser492 during mitosis, and this phosphorylation event is required for the proper loading of condensin II on chromatin. Depletion of Mps1 inhibits chromosomal targeting of condensin II and accurate chromosome condensation during prophase. These findings demonstrate that Mps1 governs chromosomal organization during the early stage of mitosis to facilitate proper chromosome segregation.
在有丝分裂过程中,基因组 DNA 会凝聚成染色体,以促进其均等分配到子细胞中。染色体的凝聚发生在细胞周期从 G2 期向有丝分裂的进展过程中。前期染色体的压缩失败会导致随后染色体的失调。然而,控制有丝分裂中期染色体凝聚的早期阶段的分子机制在很大程度上是未知的。在这里,我们显示 Mps1 调节有丝分裂过程中的初始染色体凝聚。我们确定了凝聚素 II 是一种新的 Mps1 相关蛋白。Mps1 在有丝分裂期间将凝聚素 II 的一个亚基 CAP-H2 磷酸化在 Ser492 上,该磷酸化事件对于凝聚素 II 正确加载到染色质上是必需的。Mps1 的耗竭抑制了凝聚素 II 的染色体靶向和前期的准确染色体凝聚。这些发现表明 Mps1 在有丝分裂的早期阶段控制染色体的组织,以促进正确的染色体分离。