What better measure than ribosome synthesis?: Figure 1.

Cells grow; cells divide. Some cells grow without dividing: neurons, or oocytes. Some cells divide without growing: developing zygotes. For most cells, however, growth and division are coupled, thereby maintaining cell size within narrow limits. The basis of this coupling has been elusive. Cell growth was the subject of some of the earliest molecular biological investigations when it was shown that, on a variety of media, the ribosome content of Escherichia coli was proportional to the growth rate (Maaloe and Kjeldgaard 1966). Soon thereafter, the study of growth was overshadowed by the study of gene expression with its emphasis on the regulated transcription of individual genes. More recently, the recognition that growth and cell division are so closely intertwined has led to new interest in the study of growth per se, as suggested by the recent publication of two reviews (Kozma and Thomas 2002; Saucedo and Edgar 2002) and a monograph, Cell Growth: Control of Cell Size (Hall et al. 2004). In considering cell growth and division, two points are paramount: (1) Cell growth requires the synthesis of proteins; the synthesis of proteins requires ribosomes. Thus, ultimately the control of cell growth must involve the control of ribosome synthesis. (2) A cell must somehow match the replication of its genome, with the implicit decision to divide, to its size, or perhaps to its predicted size at the time division will occur. These two aspects have often been considered in parallel, the studies of macromolecular synthesis, transcription, and translation proceeding with little care for their implications for cell division, and the studies of the intricate dance of cyclins that powers the cell cycle relatively unconcerned with the macromolecular events within the cell that ultimately drive the decision to divide. Those involved in the cell cycle, however, have been more attentive, if no more successful at understanding the mechanisms controlling the relationship between growth and division. Thus, the dean of the cell cycle field recently wrote, “The existence of a ‘size control’ is well known ... but it has been remarkably resistant to molecular analysis. ... It is a vital link coordinating cell growth with periodic events of the cycle.” (Mitchison 2003).