Polar chromosomes are rescued from missegregation by spindle elongation-driven microtubule pivoting.

Koprivec, Isabella; Štimac, Valentina; Đura, Mario; Vukušić, Kruno; Mikec, Petra; Tolić, Iva M. (2026) Polar chromosomes are rescued from missegregation by spindle elongation-driven microtubule pivoting.. Nature Communications, 17 . ISSN 2041-1723

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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 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.

Item Type:	Article
Uncontrolled Keywords:	Polar chromosomes; Spindle elongation; Microtubule pivoting; Chromosome segregation; Chromosomal instability
Subjects:	NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Molecular origins of aneuploidies in healthy and diseased human tissues-ANEUPLOIDY Iva Tolić; Nenad Pavin 855158 EK How centrosome age affects the formation, resolution, and fate of polar chromosomes Iva Tolić IPCH-2022-10-9344 HRZZ Mechanisms of mitotic spindle's adaptation to different genome sizes Iva Tolić IP-2024-05-5336 HRZZ Mehanizmi nastajanja snopova mikrotubula potrebni za sazrijevanje diobenog vretena-SpindleForm Iva Tolić; Nenad Pavin PZS-2019-02-7653 HRZZ Inovativni protokoli mikroskopije za interdisciplinarna istraživanja u biomedicini-IPSted Iva Tolić KK.01.1.1.04.0057 EK Provedba vrhunskih istraživanja u sklopu Znanstvenog centra izvrsnosti za kvantne i kompleksne sustave te reprezentacije Liejevih algebri Hrvoje Buljan KK.01.1.1.01.0004 EU
Depositing User:	Ivana Šarić
Date Deposited:	12 Nov 2026 15:31
URI:	https://fulir.irb.hr:/id/eprint/12199
DOI:	10.1038/s41467-026-69830-1

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