Journal Article

DZNE-2026-00282

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Polar chromosomes are rescued from missegregation by spindle elongation-driven microtubule pivoting.

Koprivec, I. ; Stimac, V. (First author)DZNE* ; Đura, M. ; Vukušić, K. ; Mikec, P. ; Tolić, I. M.

2026
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41467-026-69830-1

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 mono-lateral attachments, recruiting corona components and partially Mad2, but lacking Astrin. In 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 chromosomes from the 'danger zone' behind the pole, providing mechanistic insight into chromosome congression errors in cancer.

Keyword(s): Humans (MeSH) ; Spindle Apparatus: metabolism (MeSH) ; Chromosome Segregation (MeSH) ; Microtubules: metabolism (MeSH) ; Kinetochores: metabolism (MeSH) ; Kinesins: metabolism (MeSH) ; Kinesins: genetics (MeSH) ; HeLa Cells (MeSH) ; Mad2 Proteins: metabolism (MeSH) ; Cell Line, Tumor (MeSH) ; Chromosomes, Human: metabolism (MeSH) ; Centrosome: metabolism (MeSH) ; Chromosomal Instability (MeSH) ; Kinesins ; KIF11 protein, human ; Mad2 Proteins

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Contributing Institute(s):

1. Axon Growth and Regeneration (AG Bradke)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

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