Contractile peri-nuclear actomyosin network PANEM repositions chromosomes from unfavorable locations to facilitate their interaction with the mitotic spindle

For correct chromosome segregation, kinetochore-microtubule interactions must be efficiently and properly established during prometaphase. For this, the locations of chromosomes in the nucleus or relative to spindle poles are crucial: indeed, chromosomes at the nuclear periphery or behind spindle poles (polar regions) have a higher risk of missegregation in the subsequent anaphase. The actomyosin network (PANEM) is formed on the cytoplasmic side of the nuclear envelope during prophase, and its myosin-II-dependent contraction facilitates kinetochore-microtubule interaction shortly after nuclear envelope breakdown (NEBD). However, it remains unclear which step of kinetochore-microtubule interaction is facilitated by the PANEM contraction, or which chromosomes specifically benefit from it. Here we show that the PANEM contraction pushes chromosomes located at the nuclear periphery inward immediately after NEBD. This facilitates kinetochores' initial interaction with spindle microtubules, but does not affect their subsequent poleward motion. The PANEM contraction also promotes the onset of their congression towards the spindle mid-plane, but does not affect congression itself once it starts. Furthermore, the PANEM contraction reduces the volume of polar regions, and helps chromosomes exit these regions and initiate their congression. Impaired PANEM contraction results in defective chromosome congression and frequent chromosome mis-segregation. In conclusion, shortly after NEBD, the PANEM contraction repositions chromosomes from the nuclear periphery and polar regions to facilitate productive kinetochore-microtubule interaction and ensure high-fidelity chromosome segregation.