Mechanosensitive Nuclear Asymmetries Define a Bipolar Spindle Scaffold to Ensure Mitotic Fidelity

Abstract

During prophase, centrosomes need to separate and position to correctly assemble the mitotic spindle. This process occurs through the action of molecular motors, cytoskeletal networks and the nucleus. How the combined activity of these different components is spatiotemporally regulated to ensure efficient spindle assembly remains unclear. Here, we show that mitotic rounding during prophase facilitates the reorientation of the centrosomes-nucleus axis, so that centrosomes position on the shortest nuclear axis at nuclear envelope (NE) breakdown. This centrosome configuration depends on mitotic chromosome condensation that creates a mechanosensitive environment on the prophase nucleus, essential for the polarized loading of Dynein on the NE. This occurs independently of its known NE adaptors. Finally, we observe this centrosome configuration favors the establishment of an initial bipolar spindle scaffold, facilitating chromosome capture and accurate segregation, without compromising division plane orientation. We propose that chromosome segregation fidelity depends on the mechanical properties of the prophase nucleus that facilitate spindle assembly by regulating NE-Dynein localization.