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bioRxiv · 10.1101/2024.06.16.599200

Microtubule pivoting driven by spindle elongation rescues polar chromosomes to ensure faithful mitosis

Koprivec, I.·Stimac, V.·Mikec, P.·Tolic, I. M.
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Abstract

Polar chromosomes, which initially attach to the mitotic spindle behind the pole, are prone to missegregation and micronuclear entrapment, contributing to chromosomal instability in cancer. Yet, the mechanisms ensuring their faithful segregation remain unclear. Here, we show that polar chromosomes require a unique step involving spindle elongation, which repositions chromosome-bound astral microtubules by pivoting them around the centrosome toward the spindle surface. By modulating Eg5/KIF11 activity, we demonstrate that spindle elongation determines the direction and extent of pivoting, with microtubules from the opposite spindle half facilitating final movement. Kinetochores on polar chromosomes form mixed lateral and immature monotelic attachments, recruiting corona components and partially Mad2, but lacking Astrin. In several cancer cell lines, limited spindle elongation delays polar chromosome resolution, whereas enhanced elongation accelerates it. These findings highlight the role of spindle elongation in the timely rescue of polar chromosomes from the danger zone behind the pole, and provide mechanistic insight into how chromosome congression errors can arise in cancer.

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Koprivec, I., Stimac, V., Mikec, P., Tolic, I. M.. 2024-06-16. Microtubule pivoting driven by spindle elongation rescues polar chromosomes to ensure faithful mitosis. https://doi.org/10.1101/2024.06.16.599200

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