An international team of researchers led by Matteo Barberis of the UvA has discovered a mechanism that explains how cells achieve their proper timing of reproduction. Their findings have been published in the latest issue of Nature NPJ Systems Biology and Applications.
To ensure continuity of life, reproduction of cells within any organism occurs at a well-defined timing. This precise timing is such that duplication of a cell’s genetic material (a process called DNA replication) is coordinated with its transfer to descendants (a process called cell division). The aim of this study was to unravel how the timely synchronization of DNA replication with cell division is achieved. The research was conducted using the model organism budding yeast, where the control of these processes occurs similarly to human cells.
Matteo Barberis of the Swammerdam Institute of Life Science and other researchers have discovered that modulation of one specific gene is responsible for the timely activation of enzymes involved in this coordination. The researchers succeeded in the identification of this gene by using detailed mathematical models that predicted its involvement and, subsequently, by validating this prediction with biological and biochemical methodologies. The findings of the present study highlight that the order in time of enzymatic activities is required for synchronizing DNA replication with cell division, and reveal a previously unknown mechanism underlying timely cell reproduction.
Regulation of the precise timing by which cells reproduce is a major breakthrough, as its failure results in an uncontrolled, enhanced cell division that is a typical feature of tumor cells in humans. A systems biology research that integrates predictive computer models with dedicated experimental validation is pivotal to highlight mechanisms that address cellular timing. This approach pinpoints a possibly conserved principle of design of reproduction in eukaryotic organisms, including humans.
Christian Linke, Anastasia Chasapi, Alberto González-Novo, Istabrak Al Sawad, Silvia Tognetti, Edda Klipp, Mart Loog, Sylvia Krobitsch, Francesc Posas, Ioannis Xenarios and Matteo Barberis: ‘A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle’ in Nature NPJ Systems Biology and Applications, 6 March 2017