a Telomere Biology Section , LBMB, National Cancer Institute, NIH, Bethesda , MD , USA.
Cell Cycle. 2017 Aug 3;16(15):1392-1396. doi: 10.1080/15384101.2017.1338986. Epub 2017 Jul 5.
Despite its ubiquity in interphase eukaryotic nuclei, the functional significance of the RabI configuration, in which interphase centromeres are clustered at the nuclear envelope (NE) near the centrosome and telomeres localize at the opposite end of the nucleus, has remained mysterious. In a broad variety of organisms, including Schizosaccharomyces pombe, the RabI configuration is maintained throughout mitotic interphase. The fission yeast linker of nucleoskeleton and cytoskeleton (LINC) complex mediates this centromere association. The functional significance of centromere positioning during interphase has been recently revealed using a conditionally inactivated LINC allele that maintains LINC stability but releases interphase centromere-LINC contacts. Remarkably, this interphase release abolishes mitotic spindle formation. Here, we confirm these observations using an alternative strategy to explore the role of centromere-NE association without modifying the LINC complex. We analyze spindle dynamics in cells lacking Csi1, a stabilizer of centromere-LINC associations, and Lem2, a NE protein harboring lamin interacting domains. We recapitulate these observations and their implications for the functional significance of centromere positioning for cell cycle progression in fission yeast and most likely, a wide range of eukaryotes.
尽管 RabI 构型在有丝分裂间期真核核中普遍存在,但其功能意义仍然是神秘的,这种构型中,有丝分裂间期的着丝粒簇集在靠近中心体的核膜(NE)处,端粒则定位于细胞核的另一端。在包括酿酒酵母在内的广泛的生物体中,RabI 构型在整个有丝分裂间期都得到维持。裂殖酵母核骨架和细胞骨架(LINC)复合物的连接蛋白介导了这种着丝粒的关联。最近,使用一种条件失活的 LINC 等位基因,该基因维持 LINC 的稳定性但释放有丝分裂间期着丝粒-LINC 接触,揭示了间期着丝粒定位的功能意义。值得注意的是,这种间期释放会破坏有丝分裂纺锤体的形成。在这里,我们使用另一种策略来探索不改变 LINC 复合物的情况下,着丝粒-NE 关联的作用,从而证实了这些观察结果。我们分析了缺乏 Csi1(一种稳定着丝粒-LINC 关联的蛋白)和 Lem2(一种含有层粘连蛋白相互作用结构域的 NE 蛋白)的细胞中的纺锤体动力学。我们重现了这些观察结果,并探讨了它们对裂殖酵母和可能更广泛的真核生物中着丝粒定位对细胞周期进程的功能意义。