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PreprintCC BY-NC-NDbioRxiv

Spindle size scaling secures mitotic fidelity against whole-genome doubling-associated mechanical stress

  1. 1Faculty of Advanced Life Science, Hokkaido University

Abstract

Although whole-genome doubling (WGD) accompanies a drastic increase in chromosome number, post-WGD cells often continue to divide. How mitosis is sustained under increased chromosome number remains largely unknown. Here, we found that WGD cells require longer mitotic spindles than isogenic diploids to maintain spindle bipolarity. WGD increased mechanical stress on spindle poles during metaphase, associated with a higher risk of pole fragmentation. Disrupting kinetochore-microtubule attachment alleviated pole stress and fragmentation in WGD cells, suggesting that WGD-linked mechanical stress arises from spindle-chromosome interactions. Artificial spindle elongation reduced the pole stress and mitigated pole fragmentation defects in WGD cells. Our findings identify chromosome gain as a critical mechanical challenge to spindle organization and establish spindle size scaling as an adaptive mechanism that preserves mitotic fidelity after WGD.

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BibTeX
@misc{wang2026spindle,
  title = {{Spindle size scaling secures mitotic fidelity against whole-genome doubling-associated mechanical stress}},
  author = {Q. Wang and C. Watanabe and S. Ishida-Ishihara and Y. Nishimura and T. Yamamoto and F. Motegi and R. Uehara},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.09.757450},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.09.757450v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Spindle size scaling secures mitotic fidelity against whole-genome doubling-associated mechanical stress
AU  - Q. Wang
AU  - C. Watanabe
AU  - S. Ishida-Ishihara
AU  - Y. Nishimura
AU  - T. Yamamoto
AU  - F. Motegi
AU  - R. Uehara
PY  - 2026
DA  - 2026/10/09
PB  - bioRxiv
DO  - 10.64898/2026.10.09.757450
UR  - https://www.biorxiv.org/content/10.64898/2026.10.09.757450v1
AB  - Although whole-genome doubling (WGD) accompanies a drastic increase in chromosome number, post-WGD cells often continue to divide. How mitosis is sustained under increased chromosome number remains largely unknown. Here, we found that WGD cells require longer mitotic spindles than isogenic diploids to maintain spindle bipolarity. WGD increased mechanical stress on spindle poles during metaphase, associated with a higher risk of pole fragmentation. Disrupting kinetochore-microtubule attachment alleviated pole stress and fragmentation in WGD cells, suggesting that WGD-linked mechanical stress arises from spindle-chromosome interactions. Artificial spindle elongation reduced the pole stress and mitigated pole fragmentation defects in WGD cells. Our findings identify chromosome gain as a critical mechanical challenge to spindle organization and establish spindle size scaling as an adaptive mechanism that preserves mitotic fidelity after WGD.
ER  -