Ensemble-Level Organization of Human Kinetochores and Evidence for Distinct Tension and Attachment Sensors
Summary: Kinetochores are multi-protein machines that form dynamic attachments to microtubules and control chromosome segregation. High fidelity is ensured because kinetochores can monitor attachment status and tension, using this information to activate checkpoints and error-correction mechanisms....
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720304356 |
| _version_ | 1811268237116047360 |
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| author | Emanuele Roscioli Tsvetelina E. Germanova Christopher A. Smith Peter A. Embacher Muriel Erent Amelia I. Thompson Nigel J. Burroughs Andrew D. McAinsh |
| author_facet | Emanuele Roscioli Tsvetelina E. Germanova Christopher A. Smith Peter A. Embacher Muriel Erent Amelia I. Thompson Nigel J. Burroughs Andrew D. McAinsh |
| author_sort | Emanuele Roscioli |
| collection | DOAJ |
| description | Summary: Kinetochores are multi-protein machines that form dynamic attachments to microtubules and control chromosome segregation. High fidelity is ensured because kinetochores can monitor attachment status and tension, using this information to activate checkpoints and error-correction mechanisms. To explore how kinetochores achieve this, we used two- and three-color subpixel fluorescence localization to define how proteins from six major complexes (CCAN, MIS12, NDC80, KNL1, RZZ, and SKA) and the checkpoint proteins Bub1, Mad1, and Mad2 are organized in the human kinetochore. This reveals how the outer kinetochore has a high nematic order and is largely invariant to the loss of attachment or tension, except for two mechanical sensors. First, Knl1 unravels to relay tension, and second, NDC80 undergoes jackknifing and loss of nematic order under microtubule detachment, with only the latter wired up to the checkpoint signaling system. This provides insight into how kinetochores integrate mechanical signals to promote error-free chromosome segregation. : Roscioli et al. use subpixel imaging and computational methods to determine the ensemble-level 3D organization of the human kinetochore. They show how kinetochores undergo distinct rearrangements in response to the loss of attachment and tension. Keywords: mitosis, kinetochore, spindle assembly checkpoint, microtubule dynamics, Ndc80, Knl1, tension, Bayesian inference |
| first_indexed | 2024-04-12T21:18:12Z |
| format | Article |
| id | doaj.art-786ffb97659f4948ad237de50c3a4a33 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T21:18:12Z |
| publishDate | 2020-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-786ffb97659f4948ad237de50c3a4a332022-12-22T03:16:22ZengElsevierCell Reports2211-12472020-04-01314Ensemble-Level Organization of Human Kinetochores and Evidence for Distinct Tension and Attachment SensorsEmanuele Roscioli0Tsvetelina E. Germanova1Christopher A. Smith2Peter A. Embacher3Muriel Erent4Amelia I. Thompson5Nigel J. Burroughs6Andrew D. McAinsh7Centre for Mechanochemical Cell Biology, University of Warwick, Coventry, UK; Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UKCentre for Mechanochemical Cell Biology, University of Warwick, Coventry, UK; Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UKCentre for Mechanochemical Cell Biology, University of Warwick, Coventry, UK; Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UKCentre for Mechanochemical Cell Biology, University of Warwick, Coventry, UK; Mathematics Institute, University of Warwick, Coventry, UKCentre for Mechanochemical Cell Biology, University of Warwick, Coventry, UK; Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UKCentre for Mechanochemical Cell Biology, University of Warwick, Coventry, UK; Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UKCentre for Mechanochemical Cell Biology, University of Warwick, Coventry, UK; Mathematics Institute, University of Warwick, Coventry, UK; Corresponding authorCentre for Mechanochemical Cell Biology, University of Warwick, Coventry, UK; Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK; Corresponding authorSummary: Kinetochores are multi-protein machines that form dynamic attachments to microtubules and control chromosome segregation. High fidelity is ensured because kinetochores can monitor attachment status and tension, using this information to activate checkpoints and error-correction mechanisms. To explore how kinetochores achieve this, we used two- and three-color subpixel fluorescence localization to define how proteins from six major complexes (CCAN, MIS12, NDC80, KNL1, RZZ, and SKA) and the checkpoint proteins Bub1, Mad1, and Mad2 are organized in the human kinetochore. This reveals how the outer kinetochore has a high nematic order and is largely invariant to the loss of attachment or tension, except for two mechanical sensors. First, Knl1 unravels to relay tension, and second, NDC80 undergoes jackknifing and loss of nematic order under microtubule detachment, with only the latter wired up to the checkpoint signaling system. This provides insight into how kinetochores integrate mechanical signals to promote error-free chromosome segregation. : Roscioli et al. use subpixel imaging and computational methods to determine the ensemble-level 3D organization of the human kinetochore. They show how kinetochores undergo distinct rearrangements in response to the loss of attachment and tension. Keywords: mitosis, kinetochore, spindle assembly checkpoint, microtubule dynamics, Ndc80, Knl1, tension, Bayesian inferencehttp://www.sciencedirect.com/science/article/pii/S2211124720304356 |
| spellingShingle | Emanuele Roscioli Tsvetelina E. Germanova Christopher A. Smith Peter A. Embacher Muriel Erent Amelia I. Thompson Nigel J. Burroughs Andrew D. McAinsh Ensemble-Level Organization of Human Kinetochores and Evidence for Distinct Tension and Attachment Sensors Cell Reports |
| title | Ensemble-Level Organization of Human Kinetochores and Evidence for Distinct Tension and Attachment Sensors |
| title_full | Ensemble-Level Organization of Human Kinetochores and Evidence for Distinct Tension and Attachment Sensors |
| title_fullStr | Ensemble-Level Organization of Human Kinetochores and Evidence for Distinct Tension and Attachment Sensors |
| title_full_unstemmed | Ensemble-Level Organization of Human Kinetochores and Evidence for Distinct Tension and Attachment Sensors |
| title_short | Ensemble-Level Organization of Human Kinetochores and Evidence for Distinct Tension and Attachment Sensors |
| title_sort | ensemble level organization of human kinetochores and evidence for distinct tension and attachment sensors |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720304356 |
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