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Accurate chromosome segregation is vital for cell and organismal viability. The mitotic spindle, a bipolar macromolecular machine composed largely of dynamic microtubules, is responsible for chromosome segregation during each cell replication cycle. Prior to anaphase, a bipolar metaphase spindle must be formed in which each pair of chromatids is attached to microtubules from opposite spindle poles. In this bipolar configuration pulling forces from the dynamic microtubules can generate tension across the sister kinetochores. The tension status acts as a signal that can destabilize aberrant kinetochore-microtubule attachments and reinforces correct, bipolar connections. Historically it has been challenging to isolate the specific role of tension in mitotic processes due to the interdependency of attachment and tension status at kinetochores. Recent technical and experimental advances have revealed new insights into how tension functions during mitosis. Here we summarize the evidence that tension serves as a biophysical signal that unifies multiple aspects of kinetochore and centromere function to ensure accurate chromosome segregation.
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The role of kinetochore dynein in checkpoint silencing is restricted to disassembly of the corona
During mitosis, kinetochore–microtubule attachments are monitored by a molecular surveillance system known as the spindle assembly checkpoint. The prevailing model posits that dynein evicts checkpoint proteins (e.g., Mad1, Mad2) from stably attached kinetochores by transporting them away from kinetochores, thus contributing to checkpoint silencing. However, the mechanism by which dynein performs this function, and its precise role in checkpoint silencing remain unresolved. Here, we find that dynein’s role in checkpoint silencing is restricted to evicting checkpoint effectors from the fibrous corona, and not the outer kinetochore. Dynein evicts these molecules from the corona in a manner that does not require stable, end-on microtubule attachments. Thus, by disassembling the corona through indiscriminate microtubule encounters, dynein primes the checkpoint signaling apparatus so it can respond to stable end-on microtubule attachments and permit cells to progress through mitosis. Accordingly, we find that dynein function in checkpoint silencing becomes largely dispensable in cells in which checkpoint effectors are excluded from the corona.
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- Award ID(s):
- 2107444
- PAR ID:
- 10418157
- Editor(s):
- Bloom, Kerry
- Date Published:
- Journal Name:
- Molecular Biology of the Cell
- Volume:
- 34
- Issue:
- 7
- ISSN:
- 1059-1524
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1091/mbc.E23-04-0130
