Aurora B-dependent Ndc80 Degradation Regulates Kinetochore Composition in Meiosis

Chen, J.; Liao, A.; Powers, E. N.; Liao, H.; Kohlstaedt, L. A.; Evans, R.; Holly, R. M.; Kim Kim, J.; Jovanovic, M.; Unal, E.

doi:10.1101/836668

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bioRxiv · 10.1101/836668

Aurora B-dependent Ndc80 Degradation Regulates Kinetochore Composition in Meiosis

Chen, J.·Liao, A.·Powers, E. N.·Liao, H.·Kohlstaedt, L. A.·Evans, R.·Holly, R. M.·Kim Kim, J.·Jovanovic, M.·Unal, E.

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Abstract

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 have 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.

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Chen, J., Liao, A., Powers, E. N., Liao, H., Kohlstaedt, L. A., Evans, R., Holly, R. M., Kim Kim, J., Jovanovic, M., Unal, E.. 2019-11-09. Aurora B-dependent Ndc80 Degradation Regulates Kinetochore Composition in Meiosis. https://doi.org/10.1101/836668

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