TY  - JOUR
AU  - Koprivec, Isabella
AU  - Stimac, Valentina
AU  - Đura, Mario
AU  - Vukušić, Kruno
AU  - Mikec, Petra
AU  - Tolić, Iva M
TI  - Polar chromosomes are rescued from missegregation by spindle elongation-driven microtubule pivoting.
JO  - Nature Communications
VL  - 17
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2026-00282
SP  - 2049
PY  - 2026
AB  - 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.
KW  - Humans
KW  - Spindle Apparatus: metabolism
KW  - Chromosome Segregation
KW  - Microtubules: metabolism
KW  - Kinetochores: metabolism
KW  - Kinesins: metabolism
KW  - Kinesins: genetics
KW  - HeLa Cells
KW  - Mad2 Proteins: metabolism
KW  - Cell Line, Tumor
KW  - Chromosomes, Human: metabolism
KW  - Centrosome: metabolism
KW  - Chromosomal Instability
KW  - Kinesins (NLM Chemicals)
KW  - KIF11 protein, human (NLM Chemicals)
KW  - Mad2 Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41844586
C2  - pmc:PMC12996568
DO  - DOI:10.1038/s41467-026-69830-1
UR  - https://pub.dzne.de/record/285725
ER  -