Aurora B-dependent Ndc80 degradation regulates kinetochore composition in meiosis
| Autor: | Jenny Kim Kim, Marko Jovanovic, Lori A. Kohlstaedt, Ryan M. Holly, Jingxun Chen, Elçin Ünal, Rena K. Evans, Emily Nicole Powers, Hanna Liao, Andrew Liao |
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| Rok vydání: | 2020 |
| Předmět: |
proteolysis
Saccharomyces cerevisiae Proteins 1.1 Normal biological development and functioning Aurora B kinase Saccharomyces cerevisiae Protein degradation Biology Microtubules Medical and Health Sciences Chromosome segregation 03 medical and health sciences 0302 clinical medicine Prophase Meiosis Underpinning research Genetics Aurora Kinase B chromosome Aurora B Kinetochores 030304 developmental biology 0303 health sciences Kinetochore Psychology and Cognitive Sciences Nuclear Proteins Biological Sciences Spindle apparatus Cell biology APC kinetochore NDC80 Ndc80 030220 oncology & carcinogenesis Proteolysis Generic health relevance 030217 neurology & neurosurgery Outlook Research Paper Developmental Biology |
| Zdroj: | Genes & development, vol 34, iss 3-4 Genes Dev |
| Popis: | 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 APCAma1and 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. |
| Databáze: | OpenAIRE |
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