Scaling gene expression for cell size control and senescence in Saccharomyces cerevisiae
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REVIEW
Scaling gene expression for cell size control and senescence in Saccharomyces cerevisiae Yuping Chen1 · Bruce Futcher2 Received: 8 July 2020 / Revised: 8 July 2020 / Accepted: 15 July 2020 © The Author(s) 2020
Abstract Cells divide with appropriate frequency by coupling division to growth—that is, cells divide only when they have grown sufficiently large. This process is poorly understood, but has been studied using cell size mutants. In principle, mutations affecting cell size could affect the mean size (“set-point” mutants), or they could affect the variability of sizes (“homeostasis” mutants). In practice, almost all known size mutants affect set-point, with little effect on size homeostasis. One model for size-dependent division depends on a size-dependent gene expression program: Activators of cell division are over-expressed at larger and larger sizes, while inhibitors are under-expressed. At sufficiently large size, activators overcome inhibitors, and the cell divides. Amounts of activators and inhibitors determine the set-point, but the gene expression program (the rate at which expression changes with cell size) determines the breadth of the size distribution (homeostasis). In this model, set-point mutants identify cell cycle activators and inhibitors, while homeostasis mutants identify regulators that couple expression of activators and inhibitors to size. We consider recent results suggesting that increased cell size causes senescence, and suggest that at very large sizes, an excess of DNA binding proteins leads to size induced senescence. Keywords Yeast · Cell size · Cell division · Size control · G1 S transition · Start
Introduction Cells couple division to growth. Cells must neither divide more than they grow (lest they shrink to death), nor grow more than they divide (lest they explode). At least for microbes, the coupling of division to growth seems to involve measurement of cell size. Cells have a “critical size” for commitment to division (Hartwell and Unger 1977; Johnston et al. 1977). Cells smaller than critical size grow, but do not divide, while cells larger than the critical size divide, and so become smaller. The requirement for a minimum size makes division dependent upon growth, and, together with Communicated by M. Kupiec. * Bruce Futcher [email protected] Yuping Chen [email protected] 1
Department of Chemical and Systems Biology, Stanford Medicine, Stanford, CA 94305‑5174, USA
Department of Microbiology and Immunology, Stony Brook University, Stony Brook, NY 11794‑5222, USA
2
division at larger sizes, maintains cells in a reasonably narrow size range. The cell size distribution is characteristic for a cell type in a given environment. For this system, the cell must have a way of measuring size, so that the cell “knows” whether it has achieved critical size or not. Molecular biologists are familiar with mechanisms by which cells glean environmental information. The lac operon of E. coli is a mechanism for sensing lactose, while the Gal4/Gal80 system of the yeast S. c
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