ArticlebioRxiv : the preprint server for biology2025
Mammalian metaphase kinetochores are elastic and require condensin for robust structure and function.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The mammalian kinetochore connects chromosomes to dynamic spindle microtubules. To remain attached, it must maintain its structural integrity under force, but to what extent and how it does so remain unclear. Under spindle forces, we find using super resolution microscopy that inner (CENP-A) and outer (Hec1) metaphase kinetochores undergo correlated, large-scale (1 μm) deformations along the force axis, suggesting dynamic, relative sliding of parallel protein linkages. Kinetochore shape changes can be asymmetric, with centromere-facing "tails" correlating with erroneous attachment geometries. Applying microneedle pulling forces, we demonstrate that kinetochores are elastic, stretching under force and relaxing in seconds afterwards. Finally, we show that SMC2 depletion results in more variable kinetochore deformations, despite maintained elasticity, and in reduced microtubule attachment stability. Thus, the kinetochore is structurally highly dynamic and requires a stable centromere base to maintain its structure and function under force. We propose a model whereby individual protein linkages are stiff yet global kinetochore structure flexible to accommodate different attachment geometries and forces while maintaining function.
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