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首页> 外文期刊>Cell cycle >The nucleolar phosphatase Cdc14B is dispensable for chromosome segregation and mitotic exit in human cells.
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The nucleolar phosphatase Cdc14B is dispensable for chromosome segregation and mitotic exit in human cells.

机译：核仁磷酸酶Cdc14B对于人类细胞中的染色体分离和有丝分裂出口是必不可少的。

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In yeast, the protein phosphatase Cdc14 promotes chromosome segregation, mitotic exit, and cytokinesis by reversing M-phase phosphorylations catalyzed by Cdk1. A key feature of Cdc14 regulation is its sequestration within the nucleolus, which restricts its access to potential substrates for much of the cell cycle. Mammals also possess a nucleolar Cdc14 homolog, termed Cdc14B, but its roles during mitosis and cell division remain speculative. Here we analyze Cdc14B's subcellular dynamics during mitosis and rigorously test its functional contributions to cell division through homozygous disruption of the Cdc14B locus in human somatic cells. While Cdc14B is initially released from nucleoli at the start of mitosis, the phosphatase quickly redistributes onto segregating sister chromatids during anaphase. This relocalization is mainly driven by Cdk1 inactivation, as pharmacologic inhibition of Cdk1 in prometaphase cells redirects Cdc14B onto chromosomes. However, in sharp contrast to yeast cdc14 mutants, human Cdc14B(Delta/Delta) cells were viable and lacked defects in spindle assembly, anaphase progression, mitotic exit, and cytokinesis, and continued to segregate ribosomal DNA repeats with near-normal proficiency. Our findings reveal substantial divergence in mitotic regulation between yeast and mammalian cells, as the latter possess efficient mechanisms for completing late M-phase events in the absence of a nucleolar Cdc14-related phosphatase.
机译：在酵母中，蛋白磷酸酶Cdc14通过逆转Cdk1催化的M相磷酸化而促进染色体分离，有丝分裂退出和胞质分裂。 Cdc14调控的关键特征是其在核仁中的螯合，这限制了它在细胞周期的大部分时间内都接触潜在的底物。哺乳动物还拥有核仁的Cdc14同源物，称为Cdc14B，但其在有丝分裂和细胞分裂过程中的作用仍是推测性的。在这里，我们分析了Cdc14B在有丝分裂过程中的亚细胞动力学，并通过对人体细胞中Cdc14B基因座的纯合破坏，严格测试了其对细胞分裂的功能性贡献。虽然Cdc14B最初是在有丝分裂开始时从核仁释放的，但磷酸酶在后期会迅速重新分布到分离的姐妹染色单体上。这种重新定位主要是由Cdk1失活驱动的，因为前中期细胞中Cdk1的药理抑制作用将Cdc14B重定向到染色体上。但是，与酵母cdc14突变体形成鲜明对比的是，人类Cdc14B（Delta / Delta）细胞是活的，并且在纺锤体组装，后期发育，有丝分裂退出和胞质分裂方面缺乏缺陷，并且继续以接近正常的水平分离核糖体DNA重复序列。我们的发现表明酵母和哺乳动物细胞之间的有丝分裂调控存在实质性差异，因为后者具有在没有核仁Cdc14相关磷酸酶的情况下完成晚期M期事件的有效机制。

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