Contractile peri-nuclear actomyosin network repositions peripheral and polar chromosomes to promote early kinetochore–microtubule interactions

For correct segregation of chromosomes in mitosis, they must efficiently and properly interact with the mitotic spindle during prometaphase. For this, the locations of chromosomes in the nucleus or relative to spindle poles are crucial – chromosomes at the nuclear periphery or behind spindle poles (polar regions) interact less efficiently with the mitotic spindle and show higher risks of missegregation in the subsequent anaphase. Nonetheless, the missegregation rate of such chromosomes is still relatively low in unperturbed normal cells. Thus, unknown mechanisms may mitigate the risks of their missegregation. We previously found that the actomyosin network (PANEM) is formed on the cytoplasmic side of the nuclear envelope during prophase, and its myosin-II-dependent contraction facilitates chromosome interaction with the mitotic spindle, shortly after nuclear envelope breakdown (NEBD). However, it remains unclear which chromosome interaction steps are facilitated or which chromosomes specifically benefit from it. Here, we show that the PANEM contraction directly pushes chromosomes located at the nuclear periphery inward immediately after NEBD. Tracking motions of individual kinetochores reveals that the PANEM contraction 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 reposition chromosomes from these regions and initiate their congression. Impaired PANEM contraction results in defective chromosome congression and frequent chromosome missegregation. In conclusion, shortly after NEBD, the PANEM contraction repositions chromosomes from unfavorable locations, i.e. the nuclear periphery and polar regions, to facilitate productive kinetochore-microtubule interaction and ensure high-fidelity chromosome segregation.