To ensure proper segregation during mitosis, chromosomes must be efficiently captured by spindle microtubules and subsequently aligned on the mitotic spindle. The efficacy of chromosome interaction with the spindle can be influenced by how widely chromosomes are scattered in space. Here, we quantify chromosome-scattering volume (CSV) and find that it is reduced soon after nuclear envelope breakdown (NEBD) in human cells. The CSV reduction occurs primarily independently of microtubules and is therefore not an outcome of interactions between chromosomes and the spindle. We find that, prior to NEBD, an acto-myosin network is assembled in a LINC complex-dependent manner on the cytoplasmic surface of the nuclear envelope. This acto-myosin network remains on nuclear envelope remnants soon after NEBD, and its myosin-II- mediated contraction reduces CSV and facilitates timely chromosome congression and correct segregation. Thus, we find a novel mechanism that positions chromosomes in early mitosis to ensure efficient and correct chromosome–spindle interactions.
Bibliographical noteFunding Information:
Wellcome 096535/Z/11/Z Tomoyuki Tanaka Wellcome 097945/Z/11/Z Tomoyuki Tanaka Wellcome 208401/Z/17/Z Tomoyuki Tanaka Cancer Research UK C28206/A114499 Helfrid Hochegger Medical Research Council MR/K015869/1 Tomoyuki Tanaka The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
We thank Tanaka lab members, A Ciulli, A Testa, J Januschke and M Gierlinski for discussion; G Ball for help with image analysis; L Clayton for editing the manuscript;, T Fukagawa, J Swedlow, S Mega-son, R Adelstein, M Davidson, and RY Tsien for reagents; S Swift, and P Appleton for microscope maintenance. This work was supported by the Wellcome Trust (096535/Z/11/Z, 097945/Z/11/Z, 208401/Z/17/Z), Cancer Research UK (C28206/A114499) and Medical Research Council (MR/ K015869/1). TUT is a Wellcome Trust Principal Research Fellow. The authors declare no competing financial interests.
© Booth et al.