Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1Yayoi, Tokyo 113-0032, Japan.
Instituto de Biología Molecular y Celular del Cáncer (CSIC-USAL), 37007 Salamanca, Spain.
Nature. 2015 Jan 22;517(7535):466-71. doi: 10.1038/nature14097. Epub 2014 Dec 24.
The kinetochore is the crucial apparatus regulating chromosome segregation in mitosis and meiosis. Particularly in meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation) and centromeric cohesion mediated by cohesin is protected in the following anaphase. Although meiotic kinetochore factors have been identified only in budding and fission yeasts, these molecules and their functions are thought to have diverged earlier. Therefore, a conserved mechanism for meiotic kinetochore regulation remains elusive. Here we have identified in mouse a meiosis-specific kinetochore factor that we termed MEIKIN, which functions in meiosis I but not in meiosis II or mitosis. MEIKIN plays a crucial role in both mono-orientation and centromeric cohesion protection, partly by stabilizing the localization of the cohesin protector shugoshin. These functions are mediated mainly by the activity of Polo-like kinase PLK1, which is enriched to kinetochores in a MEIKIN-dependent manner. Our integrative analysis indicates that the long-awaited key regulator of meiotic kinetochore function is Meikin, which is conserved from yeasts to humans.
着丝粒是调节有丝分裂和减数分裂中染色体分离的关键装置。特别是在减数分裂 I 中，与有丝分裂不同，姐妹着丝粒被来自同一纺锤极（单定向）的微管捕获，并且由黏合蛋白介导的着丝粒黏合在随后的后期被保护。尽管减数分裂着丝粒因子仅在芽殖酵母和裂殖酵母中被鉴定出来，但这些分子及其功能被认为更早发生了分化。因此，减数分裂着丝粒调节的保守机制仍然难以捉摸。在这里，我们在小鼠中鉴定了一个减数分裂特异性着丝粒因子，我们称之为 MEIKIN，它在减数分裂 I 中发挥作用，但在减数分裂 II 或有丝分裂中不起作用。MEIKIN 在单定向和着丝粒黏合保护中都起着至关重要的作用，部分是通过稳定黏合蛋白保护蛋白 shugoshin 的定位来实现的。这些功能主要是通过富含在 MEIKIN 依赖性方式中的 Polo 样激酶 PLK1 的活性来介导的。我们的综合分析表明，长期以来一直被期待的减数分裂着丝粒功能的关键调节剂是 Meikin，它从酵母到人类都是保守的。
