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

Polar chromosomes represent a subset of ∼7 chromosomes in human cells that first 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, their mechanism of congression remains elusive. By using stimulated emission depletion (STED) and lattice light-sheet (LLS) microscopy, here we show 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 that persist throughout the process. By altering the kinesin-5 Eg5/KIF11 activity to reverse, restore, or block spindle elongation, we show that spindle elongation drives the pivoting and dictates its direction and magnitude. We reveal impaired spindle elongation as a major cause of congression defects and segregation errors of polar chromosomes in RPE1 cells after Mps1 kinase inhibition, and in the high-grade serous ovarian carcinoma OVSAHO cells. Increasing spindle elongation efficiency by depleting the kinesin-4 KIF4A rescued polar chromosomes in OVSAHO cells, supporting the causal relationship between spindle elongation and resolution of polar chromosomes. We conclude that polar chromosomes depend on spindle elongation to propel the pivoting of their astral microtubules, enabling their contact with the spindle surface, congression, and proper segregation. In the context of disease, our findings suggest that altering spindle elongation has the potential to modify mitotic errors in certain cancer cells.