Abstract
In preparation for mitosis, cells undergo extensive reorganization of the cytoskeleton and nucleus, so that chromosomes can be efficiently segregated into two daughter cells. Coordination of these cytoskeletal and nuclear events occurs through biochemical regulatory pathways, orchestrated by Cyclin-CDK activity. However, recent studies provide evidence that physical forces are also involved in the early steps of spindle assembly. Here, we will review how the crosstalk of physical forces and biochemical signals coordinates nuclear and cytoplasmic events during the G2-M transition, to ensure efficient spindle assembly and faithful chromosome segregation.
Highlights
An efficient mitosis is required to maintain genomic stability and ensure correct tissue development and homeostasis
Inside the nucleus, CDK1 contributes to nuclear pore complex (NPC) disassembly (Linder et al, 2017) and nuclear lamina (NL) depolymerization (Heald and McKeon, 1990; Peter et al, 1990)
High cellular tension triggers a transition from G1 to S phase (Huang et al, 1998; Uroz et al, 2018; Aureille et al, 2019) and regulates the length of the S-G2 phases of the cell cycle (Vitiello et al, 2019). This could be due to tension-generated nuclear envelope (NE) deformation that is sufficient to trigger mechanically-activated transcriptional programs (Aureille et al, 2019) and affect cell proliferation (Versaevel et al, 2012)
Summary
An efficient mitosis is required to maintain genomic stability and ensure correct tissue development and homeostasis. A failure in mitotic cell rounding triggered by either blocking FA disassembly or mechanical compression leads to defects in spindle assembly and mitotic progression (Lancaster et al, 2013; Nunes et al, 2020) and increases chromosome missegregation (Tse et al, 2012; Lancaster et al, 2013; Cattin et al, 2015; Matthews et al, 2020).
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