{"paper_id":"312c0304-2974-4ac8-8ea8-f528c16561e1","body_text":"Microtubule pivoting driven by spindle elongation rescues polar chromosomes to ensure faithful mitosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Article Microtubule pivoting driven by spindle elongation rescues polar chromosomes to ensure faithful mitosis Iva Tolić, Isabella Koprivec, Valentina Stimac, Petra Mikec This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4647251/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Mar, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Polar chromosomes represent a subset of ~7 chromosomes in human cells that initially attach to the mitotic spindle behind the spindle pole. These chromosomes are delayed in congression to the metaphase plate and prone to segregation errors. Yet, the mechanism of their congression remains elusive. Here we show, using stimulated emission depletion and lattice light-sheet microscopy, that polar chromosomes require a unique congression step to transit across the spindle pole. This step occurs independently of the known congression drivers, including CENP-E, kinetochore dynein, chromokinesins, and actomyosin. Instead, it relies on the pivoting of chromosome-carrying astral microtubules around the centrosome towards the spindle surface. During pivoting, polar chromosomes form complex attachments with astral microtubules, which persist throughout the process. By modulating the activity of the kinesin-5 Eg5/KIF11 to reverse, restore, or block spindle elongation, we demonstrate that spindle elongation drives the pivoting and dictates its direction and magnitude. We identify impaired spindle elongation as a major cause of mitotic errors of polar chromosomes in RPE1 cells following Mps1 kinase inhibition, and in high-grade serous ovarian carcinoma OVSAHO cells. Increasing spindle elongation through depletion of the kinesin-4 KIF4A rescues polar chromosomes in OVSAHO cells, supporting the causal relationship between spindle elongation and the resolution of polar chromosomes. We conclude that polar chromosomes depend on spindle elongation to propel the pivoting of their astral microtubules, enabling chromosome contact with the spindle surface, congression, and accurate segregation. In the context of disease, our findings suggest that manipulating spindle elongation has the potential to modify mitotic errors in certain cancer cells. Biological sciences/Cell biology/Cell division/Mitosis Biological sciences/Cell biology/Cytoskeleton/Microtubules Biological sciences/Biophysics/Motility/Intracellular movement Biological sciences/Cell biology/Cell division/Mitotic spindle Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Video1.mp4 Video 1. Video2.mp4 Video 2. Video3.mp4 Video 3. Video4.mp4 Video 4. Video5.mp4 Video 5. Video6.mp4 Video 6. Video7.mp4 Video 7. Video8.mp4 Video 8. Video9.mp4 Video 9. Cite Share Download PDF Status: Published Journal Publication published 17 Mar, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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