Abstract
The extent and dynamics of animal cell biomass accumulation during mitosis are unknown, primarily because growth has not been quantified with sufficient precision and temporal resolution. Using the suspended microchannel resonator and protein synthesis assays, we quantify mass accumulation and translation rates between mitotic stages on a single-cell level. For various animal cell types, growth rates in prophase are commensurate with or higher than interphase growth rates. Growth is only stopped as cells approach metaphase-to-anaphase transition and growth resumes in late cytokinesis. Mitotic arrests stop growth independently of arresting mechanism. For mouse lymphoblast cells, growth in prophase is promoted by CDK1 through increased phosphorylation of 4E-BP1 and cap-dependent protein synthesis. Inhibition of CDK1-driven mitotic translation reduces daughter cell growth. Overall, our measurements counter the traditional dogma that growth during mitosis is negligible and provide insight into antimitotic cancer chemotherapies.
Highlights
Animal cell growth, i.e. biomass accumulation (Lloyd, 2013), is classically viewed to take place during interphase
Animal cells grow during mitosis and cytokinesis
suspended microchannel resonator (SMR) is a microfluidic cantilever that is capable of measuring buoyant mass of single cells with a precision of
Summary
I.e. biomass accumulation (Lloyd, 2013), is classically viewed to take place during interphase. 2018; Parsons and Spencer, 1997; Prescott and Bender, 1962), and ribosomal RNA synthesis is blocked as the nucleolus disappears in prometaphase (Hernandez-Verdun, 2011). Protein synthesis has been reported to be suppressed in cell populations enriched for mitosis (Bonneau and Sonenberg, 1987; Celis et al, 1990; Fan and Penman, 1970; Prescott and Bender, 1962; Pyronnet et al, 2001; Sivan et al, 2011; Sivan et al, 2007). Polysome and ribosome profiling studies have suggested that the translational efficiency of most mRNAs is reduced in mitosis (Park et al, 2016; Qin and Sarnow, 2004; Stumpf et al, 2013; Tanenbaum et al., 2015). Studies on individual components of the translational machinery, such as eukaryotic
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