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Ki-67 和凝聚素通过不同的机制支持有丝分裂染色体的完整性。

Ki-67 and condensins support the integrity of mitotic chromosomes through distinct mechanisms.

机构信息

Cellular Dynamics Laboratory, RIKEN, Wako 351-0198, Japan

Chromosome Dynamics Laboratory, RIKEN, Wako 351-0198, Japan.

出版信息

J Cell Sci. 2018 Mar 22;131(6):jcs212092. doi: 10.1242/jcs.212092.

Abstract

Although condensins play essential roles in mitotic chromosome assembly, Ki-67 (also known as MKI67), a protein localizing to the periphery of mitotic chromosomes, had also been shown to make a contribution to the process. To examine their respective roles, we generated a set of HCT116-based cell lines expressing Ki-67 and/or condensin subunits that were fused with an auxin-inducible degron for their conditional degradation. Both the localization and the dynamic behavior of Ki-67 on mitotic chromosomes were not largely affected upon depletion of condensin subunits, and vice versa. When both Ki-67 and SMC2 (a core subunit of condensins) were depleted, ball-like chromosome clusters with no sign of discernible thread-like structures were observed. This severe defective phenotype was distinct from that observed in cells depleted of either Ki-67 or SMC2 alone. Our results show that Ki-67 and condensins, which localize to the external surface and the central axis of mitotic chromosomes, respectively, have independent yet cooperative functions in supporting the structural integrity of mitotic chromosomes.

摘要

虽然凝聚素在有丝分裂染色体组装中发挥着重要作用,但 Ki-67(也称为 MKI67),一种定位在有丝分裂染色体外周的蛋白质,也被证明对该过程有贡献。为了研究它们各自的作用,我们生成了一组基于 HCT116 的细胞系,表达 Ki-67 和/或与生长素诱导的降解结构域融合的凝聚素亚基,用于条件性降解。Ki-67 在有丝分裂染色体上的定位和动态行为在凝聚素亚基耗尽时并没有受到很大影响,反之亦然。当 Ki-67 和 SMC2(凝聚素的核心亚基)都被耗尽时,观察到没有明显线状结构的球状染色体簇。这种严重的缺陷表型与单独耗尽 Ki-67 或 SMC2 的细胞观察到的表型明显不同。我们的结果表明,分别定位于有丝分裂染色体外表面和中心轴的 Ki-67 和凝聚素在支持有丝分裂染色体的结构完整性方面具有独立但协作的功能。

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