Differential requirements for the CENP-O complex reveal parallel PLK1 kinetochore recruitment pathways
| Autor: | Marie Diane Fadel, Alexandra L. Nguyen, Iain M. Cheeseman |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cell division
Chromosomal Proteins Non-Histone Centromere Cell BUB1 Mitosis Cell Cycle Proteins Computational biology Protein Serine-Threonine Kinases Biology PLK1 Histones Chromosome segregation 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Chromosome Segregation Proto-Oncogene Proteins medicine Humans Kinetochores Molecular Biology 030304 developmental biology 0303 health sciences Kinetochore Articles Cell Biology medicine.anatomical_structure 030220 oncology & carcinogenesis Function (biology) Protein Binding |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e20-11-0751 |
| Popis: | Similar to other core biological processes, the vast majority of cell division components are essential for viability across human cell lines. However, genome-wide screens have identified a number of proteins that exhibit cell line-specific essentiality. Defining the behaviors of these proteins is critical to our understanding of complex biological processes. Here, we harness differential essentiality to reveal the contributions of the 4-subunit centromere-localized CENP-O complex, whose precise function has been difficult to define. Our results support a model in which the CENP-O complex and BUB1 act in parallel pathways to recruit a threshold level of PLK1 to mitotic kinetochores, ensuring accurate chromosome segregation. We demonstrate that targeted changes to either pathway sensitizes cells to the loss of the other component, resulting in cell-state dependent requirements. This approach also highlights the advantage of comparing phenotypes across diverse cell lines to define critical functional contributions and behaviors that could be exploited for the targeted treatment of disease. |
| Databáze: | OpenAIRE |
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