Importin-β1 functions as a chromatin sensor to position the contractile ring for cytokinesis

Cytokinesis, thefinal step of cell division, relies on the ingression of a carefully positioned actomyosin ring. Chromatin-associated Ran-GTP helps position this ring although the mechanism is not clear. We hypothesize that a depleted zone of Ran-GTP between the segregating chromosomes causes importins to become equatorially enriched and promote the recruitment of the scaffold protein anillin. However, the role of importins during anaphase remains unclear. Here, we tested if importins respond to the chromatin-associated Ran-GTP gradient to regulate ring assembly. Using endogenous tagging, live-cell imaging, and optogenetic perturbations, we found that importin-β1 becomes equatorially enriched and is required for cytokinesis in hypotriploid HeLa cells, but not in euploid HCT 116 cells. A predictive model of the Ran-GTP gradient and Ran-free importin-β1, validated experimentally by FLIM-FRET, identified factors that modulate this chromatin sensing pathway including chromatin-to-cell size ratio. Ourfindings suggest that highly aneuploid cancer cells may depend on importin-mediated anillin recruitment, representing a targetable weakness that distinguishes them from diploid cells.