Growth and division—not a one-way road
Introduction
All organisms, from single-celled bacteria and yeast, to multi-cellular organisms can vary and adjust the size of their cells, to optimize growth, storage, regenerative capacity, or production capacity [2]. It is well established that cells need to reach a crucial size in order to initiate a new cell cycle, although there are specific exceptions in multi-cellular organisms (reviewed in [1, 3]). If growth is inhibited by starvation or by chemical inhibitors of macromolecular synthesis, cells stop proliferating. In the presence of nutrients or appropriate intracellular cues, cell growth is stimulated by the activity of the Tor and RAS pathways, and cell division can occur (reviewed in [4, 5, 6]). The regulation of proliferation by growth has been extensively covered recently and we wish to direct the readers to the following excellent reviews and books on this topic [1, 2, 4, 7, 8, 9]. This review will focus on recent advances in understanding how cell cycle transitions affect growth in eukaryotes and discuss the importance of this regulation.
Section snippets
Growth rate changes at multiple points during the cell cycle of Schizosaccharomyces pombe
The rod-shaped yeast Schizosaccharomyces pombe grows by elongation at the cell poles (Figure 1a). Microscopic size measurements of S. pombe cells showed that the growth rate changes during the cell cycle. These points of change are called the Rate Change Points (RCPs) [10, 11]. After cell division each daughter cell is half the size of the mother and should therefore grow at half the rate of the mother cell. This is not the case. The newly born daughter cells grow faster than half the rate of
Actin polarization limits cell growth in budding yeast
Several studies of the growth of the budding yeast Saccharomyces cerevisiae indicate that growth is constant throughout the cell cycle. Protein synthesis does not appear to vary during the cell cycle [18]. Measurement of a protein synthesis reporter in single cells or measurement of growth by estimating cell volumes by microscopy of synchronized cultures supported this conclusion [19, 20]. Other studies reported growth rate changes during the cell cycle [21, 22]. By examining dry cell mass by
Cell cycle regulated growth in mammalian cells
Growth properties during the cell cycle have also been examined in mammalian cells. These studies demonstrated that RNA and protein synthesis varies during the cell cycle, with a sharp decrease in both taking place during mitosis [35]. The transcriptional downregulation is thought to be owing to chromosome condensation [36], the decrease in translation is owing to the switch from cap-dependent to cap-independent translation [37]. This change is mediated by inhibiting components of cap-dependent
Conclusions and outlook
Maintaining the proper growth rate at the proper stage of the cell cycle (‘balanced growth’ [12]) is a fundamental property of cells that needs to be regulated in order to maintain a constant cell size. Observations from various model systems indicate that progression through the cell cycle affects growth rate. Furthermore it appears that growth is maximal during the major GAP phase of an organism—G1 in budding yeast and mammalian cells and G2 in S. pombe. Why would cells separate the maximal
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
This work is supported by 1-U54-CA143874-01 NIH grant to AA and American Cancer Society Fellowship to AG. AA is also an investigator of the Howard Hughes Medical Institute. We thank members of the Amon lab for useful comments and suggestions regarding the manuscript.
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