Aurora B-dependent Ndc80 degradation regulates kinetochore composition in meiosis

作者：Jingxun Chen, A. L. Liao, Emily Nicole Powers, Hanna Liao, Lori A. Kohlstaedt, Rena K. Evans, Ryan M. Holly, Jenny Kim Kim, Marko Jovanović, Elçin Ünal · 发表于：Genes & Development · 年份：2020 · DOI：10.1101/gad.333997.119 · 被引用次数：26 · 研究领域：Microtubule and mitosis dynamics、Fungal and yeast genetics research、DNA Repair Mechanisms

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 APC Ama1 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.