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Individual kinetochore-fibers locally dissipate force to maintain robust mammalian spindle structure

View ORCID ProfileAlexandra F. Long, View ORCID ProfilePooja Suresh, View ORCID ProfileSophie Dumont
doi: https://doi.org/10.1101/846154
Alexandra F. Long
1Tetrad Graduate Program, University of California, San Francisco
3Department of Cell and Tissue Biology, University of California, San Francisco
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  • For correspondence: sophie.dumont@ucsf.edu a.fitz.long@gmail.com
Pooja Suresh
2Biophysics Graduate Program, University of California, San Francisco
3Department of Cell and Tissue Biology, University of California, San Francisco
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Sophie Dumont
1Tetrad Graduate Program, University of California, San Francisco
2Biophysics Graduate Program, University of California, San Francisco
3Department of Cell and Tissue Biology, University of California, San Francisco
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  • For correspondence: sophie.dumont@ucsf.edu a.fitz.long@gmail.com
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Abstract

At cell division, the mammalian kinetochore binds many spindle microtubules that make up the kinetochore-fiber. To segregate chromosomes, the kinetochore-fiber must be dynamic and generate and respond to force. Yet, how it remodels under force remains poorly understood. Kinetochore-fibers cannot be reconstituted in vitro, and exerting controlled forces in vivo remains challenging. Here, we use microneedles to pull on mammalian kinetochore-fibers and probe how sustained force regulates their dynamics and structure. We show that force lengthens kinetochore-fibers by persistently favoring plus-end polymerization, not by increasing polymerization rate. We demonstrate that force suppresses depolymerization at both plus- and minus-ends, rather than sliding microtubules within the kinetochore-fiber. Finally, we observe that kinetochore-fibers break but do not detach from kinetochores or poles. Together, this work suggests an engineering principle for spindle structural homeostasis: different physical mechanisms of local force dissipation by the k-fiber limit force transmission to preserve robust spindle structure. These findings may inform how other dynamic, force-generating cellular machines achieve mechanical robustness.

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Posted November 18, 2019.
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Individual kinetochore-fibers locally dissipate force to maintain robust mammalian spindle structure
Alexandra F. Long, Pooja Suresh, Sophie Dumont
bioRxiv 846154; doi: https://doi.org/10.1101/846154
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Individual kinetochore-fibers locally dissipate force to maintain robust mammalian spindle structure
Alexandra F. Long, Pooja Suresh, Sophie Dumont
bioRxiv 846154; doi: https://doi.org/10.1101/846154

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