title: Positive Feedback Keeps Duration of Mitosis Temporally Insulated from Upstream Cell-Cycle Events.
abstract: Cell division is characterized by a sequence of events by which a cell gives rise to two daughter cells. Quantitative measurements of cell-cycle dynamics in single cells showed that despite variability in G1-, S-, and G2 phases, duration of mitosis is short and remarkably constant. Surprisingly, there is no correlation between cell-cycle length and mitotic duration, suggesting that mitosis is temporally insulated from variability in earlier cell-cycle phases. By combining live cell imaging and computational modeling, we showed that positive feedback is the molecular mechanism underlying the temporal insulation of mitosis. Perturbing positive feedback gave rise to a sluggish, variable entry and progression through mitosis and uncoupled duration of mitosis from variability in cell cycle length. We show that positive feedback is important to keep mitosis short, constant, and temporally insulated and anticipate it might be a commonly used regulatory strategy to create modularity in other biological systems.
authors: Quantitative Cell Biology Lab, MRC-Clinical Sciences Centre (CSC), London W12 0NN, UK; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London SW7 2AZ, UK.
authors: Ana Rita
authors: AR
authors: Araujo
authors: Laboratory of Dynamics in Biological Systems, Department of Cellular and Molecular Medicine, University of Leuven, 3000 Leuven, Belgium.
authors: Lendert
authors: L
authors: Gelens
authors: Quantitative Cell Biology Lab, MRC-Clinical Sciences Centre (CSC), London W12 0NN, UK; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London SW7 2AZ, UK; European Bioinformatics Institute, EMBL-EBI, Hinxton, Cambridge CB10 1SD, UK.
authors: Rahuman S M
authors: RS
authors: Sheriff
authors: Quantitative Cell Biology Lab, MRC-Clinical Sciences Centre (CSC), London W12 0NN, UK; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London SW7 2AZ, UK. Electronic address: silvia.santos@imperial.ac.uk.
authors: Silvia D M
authors: SD
authors: Santos
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D025461:Feedback, Physiological; D016195:G2 Phase / Q000235:genetics; D006367:HeLa Cells; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008938:Mitosis; D015233:Models, Statistical; D057054:Molecular Imaging; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D000097573:Red Fluorescent Protein
chemical_list: D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D006657:Histones; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000097573:Red Fluorescent Protein; C054562:yellow fluorescent protein, Bacteria
keywords: cell division; mitosis; positive feedback; quantitative biology; temporal control