The Bub1-TPR Domain Interacts Directly with Mad3 to Generate Robust Spindle Checkpoint Arrest
| Autor: | Kevin G. Hardwick, Lucile Grzesiak, Yingrui Ma, Ioanna Leontiou, Bethan Medina-Pritchard, Karen M. May, Sue Biggins, A. Arockia Jeyaprakash, Priya Amin, Nitobe London |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Proteins Mad1 BUB3 TPR domain BUB1 Cell Cycle Proteins Saccharomyces cerevisiae Biology Protein Serine-Threonine Kinases General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Schizosaccharomyces Tetratricopeptide Repeat Mps1 Anaphase mitosis Kinetochore Mitotic checkpoint complex Nuclear Proteins 3. Good health Cell biology Spindle checkpoint 030104 developmental biology Securin spindle checkpoint M Phase Cell Cycle Checkpoints Bub1 Mad3 Schizosaccharomyces pombe Proteins General Agricultural and Biological Sciences 030217 neurology & neurosurgery |
| Zdroj: | Current Biology Leontiou, I, London, N, May, K M, Ma, Y, Grzesiak, L, Medina-Pritchard, B, Amin, P, Jeyaprakash, A A, Biggins, S & Hardwick, K G 2019, ' The Bub1-TPR domain interacts directly with Mad3 to generate robust spindle checkpoint arrest ', Current biology : CB, vol. 29, no. 14 . https://doi.org/10.1016/j.cub.2019.06.011 |
| ISSN: | 1879-0445 0960-9822 |
| DOI: | 10.1016/j.cub.2019.06.011 |
| Popis: | Summary The spindle checkpoint monitors kinetochore-microtubule interactions and generates a “wait anaphase” delay when any defects are apparent [1, 2, 3]. This provides time for cells to correct chromosome attachment errors and ensure high-fidelity chromosome segregation. Checkpoint signals are generated at unattached chromosomes during mitosis. To activate the checkpoint, Mps1Mph1 kinase phosphorylates the kinetochore component KNL1Spc105/Spc7 on conserved MELT motifs to recruit Bub3-Bub1 complexes [4, 5, 6] via a direct Bub3 interaction with phospho-MELT motifs [7, 8]. Mps1Mph1 then phosphorylates Bub1, which strengthens its interaction with Mad1-Mad2 complexes to produce a signaling platform [9, 10]. The Bub1-Mad1 platform is thought to recruit Mad3, Cdc20, and Mad2 to produce the mitotic checkpoint complex (MCC), which is the diffusible wait anaphase signal [9, 11, 12]. The MCC binds and inhibits the mitotic E3 ubiquitin ligase, known as Cdc20-anaphase promoting complex/cyclosome (APC/C), and stabilizes securin and cyclin to delay anaphase onset [13, 14, 15, 16, 17]. Here we demonstrate, in both budding and fission yeast, that kinetochores and KNL1Spc105/Spc7 can be bypassed; simply inducing heterodimers of Mps1Mph1 kinase and Bub1 is sufficient to trigger metaphase arrest that is dependent on Mad1, Mad2, and Mad3. We use this to dissect the domains of Bub1 necessary for arrest, highlighting the need for Bub1-CD1, which binds Mad1 [9], and Bub1’s highly conserved N-terminal tetratricopeptide repeat (TPR) domain [18, 19]. We demonstrate that the Bub1 TPR domain is both necessary and sufficient to bind and recruit Mad3. We propose that this brings Mad3 into close proximity to Mad1-Mad2 and Mps1Mph1 kinase, enabling efficient generation of MCC complexes. Graphical Abstract Highlights • Heterodimers of Mps1 and Bub1 generate robust spindle checkpoint arrest in yeasts • This arrest is independent of kinetochores but requires Bub1-CD1 and the Bub1-TPR • The Bub1-TPR is both necessary and sufficient for Mad3 interaction and recruitment • Recombinant fission yeast Bub1-TPR and Mad3 form a stable complex Leontiou et al. demonstrate that heterodimers of Mps1 and Bub1 are sufficient to trigger checkpoint-dependent metaphase arrest in both budding and fission yeast; kinetochores and KNL1 can be bypassed. The S. pombe Bub1-TPR domain is both necessary and sufficient to bind and recruit Mad3, enabling efficient generation of MCC complexes. |
| Databáze: | OpenAIRE |
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