Jingxun Chen, Andrew Liao, Emily N Powers, Hanna Liao, Lori A Kohlstaedt, Rena Evans, Ryan M Holly, Jenny Kim Kim, Marko Jovanovic, Elçin Ünal
Genes & development 2020 Feb 01The 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. © 2020 Chen et al.; Published by Cold Spring Harbor Laboratory Press.
Jingxun Chen, Andrew Liao, Emily N Powers, Hanna Liao, Lori A Kohlstaedt, Rena Evans, Ryan M Holly, Jenny Kim Kim, Marko Jovanovic, Elçin Ünal. Aurora B-dependent Ndc80 degradation regulates kinetochore composition in meiosis. Genes & development. 2020 Feb 01;34(3-4):209-225
PMID: 31919192
View Full Text