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Aurora B-dependent Ndc80 degradation regulates kinetochore composition in meiosis.
Genes & Development ( IF 10.5 ) Pub Date : 2020-01-09 , DOI: 10.1101/gad.333997.119
Jingxun Chen 1 , Andrew Liao 1 , Emily N Powers 1 , Hanna Liao 1 , Lori A Kohlstaedt 2 , Rena Evans 3 , Ryan M Holly 1 , Jenny Kim Kim 4 , Marko Jovanovic 4 , Elçin Ünal 1
Affiliation  

The kinetochore complex is a conserved machinery that connects chromosomes to spindle microtubules. During meiosis, the kinetochore is restructured to accommodate a specialized chromosome segregation pattern. In budding yeast, meiotic kinetochore remodeling is mediated by the temporal changes in the abundance of a single subunit called Ndc80. We previously described the regulatory events that control the timely synthesis of Ndc80. Here, we report that Ndc80 turnover is also tightly regulated in meiosis: Ndc80 degradation is active in meiotic prophase, but not in metaphase I. Ndc80 degradation depends on the ubiquitin ligase APCAma1 and is mediated by the proteasome. Importantly, Aurora B-dependent Ndc80 phosphorylation, a mark that has been previously implicated in correcting erroneous microtubule-kinetochore attachments, is essential for Ndc80 degradation in a microtubule-independent manner. The N terminus of Ndc80, including a 27-residue sequence and Aurora B phosphorylation sites, is both necessary and sufficient for kinetochore protein degradation. Finally, defects in Ndc80 turnover predispose meiotic cells to chromosome mis-segregation. Our study elucidates the mechanism by which meiotic cells modulate their kinetochore composition through regulated Ndc80 degradation, and demonstrates that Aurora B-dependent regulation of kinetochores extends beyond altering microtubule attachments.

中文翻译:

极光B依赖Ndc80降解调节减数分裂中的线粒体组成。

线粒体复合物是一种保守的机制,可将染色体连接到纺锤体微管。在减数分裂期间,将线粒体重组以适应特定的染色体分离模式。在发芽的酵母中,减数分裂的线粒体重塑由称为Ndc80的单个亚基的丰度的时间变化介导。先前我们描述了控制Ndc80及时合成的调控事件。在这里,我们报道在减数分裂中Ndc80的转换也受到严格的调节:Ndc80降解在减数分裂前期活跃,但在中期I中不活跃。Ndc80降解取决于泛素连接酶APCAma1,并由蛋白酶体介导。重要的是,Aurora B依赖的Ndc80磷酸化是一种标记,该标记先前与纠正错误的微管-动粒附着有关,对于Ndc80以微管独立的方式降解至关重要。Ndc80的N末端(包括一个27个残基的序列和Aurora B磷酸化位点)对于线粒体蛋白降解既必要又充分。最后,Ndc80周转中的缺陷使减数分裂细胞易于发生染色体错误分离。我们的研究阐明了减数分裂细胞通过调节Ndc80降解来调节其线粒体组成的机制,并证明了Aurora B依赖性的动植物调节不仅限于改变微管附着。Ndc80周转中的缺陷使减数分裂细胞易于发生染色体错误分离。我们的研究阐明了减数分裂细胞通过调节Ndc80降解来调节其线粒体组成的机制,并证明了Aurora B依赖性的动植物调节不仅限于改变微管附着。Ndc80周转中的缺陷使减数分裂细胞易于发生染色体错误分离。我们的研究阐明了减数分裂细胞通过调节Ndc80降解来调节其线粒体组成的机制,并证明了Aurora B依赖性的动植物调节不仅限于改变微管附着。
更新日期:2020-01-09
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