Mechanosensitive control of mitotic entry

As cells prepare to divide, they must ensure that enough space is available to assemble the mitotic machinery without perturbing tissue homeostasis¹. To do so, cells undergo a series of biochemical reactions regulated by cyclin B1-CDK1 that trigger the reorganization of the actomyosin cytoskeleton² and ensure the coordination of cytoplasmic and nuclear events³.

Along with the biochemical events that control mitotic entry, mechanical forces have recently emerged as important players in the regulation of cell cycle events^4–6. However, the exact link between mechanical forces and the biochemical pathways that control mitotic progression remains to be established. Here, we identify a mechanical signal on the nucleus that helps set the time for nuclear envelope permeabilization (NEP) and mitotic entry. This signal relies on actomyosin contractility, which leads to nuclear unfolding during the G2-M transition, activating the stretch-sensitive cPLA2 on the nuclear envelope. This contributes to the spatiotemporal translocation of cyclin B1 to the nucleus. Our data demonstrate how nuclear mechanics during the G2-M transition contribute to timely and efficient mitotic spindle assembly and prevents chromosomal instability.