Kinetochore-associated Stu2 promotes chromosome biorientation in vivo
| Autor: | Luke M. Rice, Matthew P. Miller, Elisabeth A. Geyer, Trisha N. Davis, Charles L. Asbury, Sue Biggins, Rena K. Evans, Michael J. MacCoss, Alex Zelter |
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| Rok vydání: | 2019 |
| Předmět: |
Atmospheric Phenomena
Cancer Research Atmospheric Science Cell division Yeast and Fungal Models Plant Science QH426-470 medicine.disease_cause Microtubules Biochemistry Chromosome segregation 0302 clinical medicine Aurora Kinases Chromosome Segregation Cell Cycle and Cell Division Plant Hormones Kinetochores Genetics (clinical) Cytoskeleton 0303 health sciences Mutation Aurora Kinetochore Plant Biochemistry Eukaryota Cell biology Precipitation Techniques Experimental Organism Systems Cell Processes Cellular Structures and Organelles Microtubule-Associated Proteins Research Article Saccharomyces cerevisiae Proteins Biorientation Aurora B kinase Saccharomyces cerevisiae Biology Research and Analysis Methods 03 medical and health sciences Saccharomyces Model Organisms Protein Domains Microtubule Genetics medicine Immunoprecipitation Molecular Biology Metaphase Ecology Evolution Behavior and Systematics 030304 developmental biology Organisms Fungi Biology and Life Sciences Proteins Cell Biology Hormones Yeast Earth Sciences Animal Studies Auxins 030217 neurology & neurosurgery |
| Zdroj: | PLoS Genetics PLoS Genetics, Vol 15, Iss 10, p e1008423 (2019) |
| ISSN: | 1553-7404 |
| Popis: | Accurate segregation of chromosomes to daughter cells is a critical aspect of cell division. It requires the kinetochores on duplicated chromosomes to biorient, attaching to microtubules from opposite poles of the cell. Bioriented attachments come under tension, while incorrect attachments lack tension and must be released to allow proper attachments to form. A well-studied error correction pathway is mediated by the Aurora B kinase, which destabilizes low tension-bearing attachments. We recently discovered that in vitro, kinetochores display an additional intrinsic tension-sensing pathway that utilizes Stu2. The contribution of kinetochore-associated Stu2 to error correction in cells, however, was unknown. Here, we identify a Stu2 mutant that abolishes its kinetochore function and show that it causes biorientation defects in vivo. We also show that this Stu2-mediated pathway functions together with the Aurora B-mediated pathway. Altogether, our work indicates that cells employ multiple pathways to ensure biorientation and the accuracy of chromosome segregation. Author summary The precise regulation of cell division is critical to processes such as self-renewal, proliferation and development. A key event in the cell cycle is the partitioning of every pair of duplicated chromosomes to daughter cells. Defects in chromosome partitioning lead to aneuploidy, a condition that is a common hallmark of cancer cells and the cause of some birth defects. Chromosomes segregate using their kinetochores, the specialized protein structures that are assembled on centromeric DNA sequences and attach to spindle microtubules. Here, we report that a protein that associates with kinetochores called Stu2 ensures that each kinetochore attaches to the proper microtubules. We identified a Stu2 mutant that does not associate with kinetochores and found that it generates aneuploidy. Together, our work identifies a previously unknown mechanism where cells ensure that chromosomes are accurately inherited during cell division. |
| Databáze: | OpenAIRE |
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