Aurora B-dependent Ndc80 degradation regulates kinetochore composition in meiosis

  1. Elçin Ünal1
  1. 1Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA;
  2. 2UC Berkeley QB3 Proteomics Facility, University of California at Berkeley, Berkeley, California 94720, USA;
  3. 3Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA;
  4. 4Department of Biology, Columbia University, New York City, New York 10027, USA
  1. Corresponding author: elcin{at}berkeley.edu

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 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.

Keywords

Footnotes

  • Received October 18, 2019.
  • Accepted December 12, 2019.

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