How cell growth triggers cell division

Cell size is fundamental to function in different cell types across the human body because it sets the scale of organelle structures, biosynthesis, and surface transport. Tiny lymphocytes squeeze through tight spaces to reach sites of infection, while the four orders of magnitude larger oocyte divides without growth to form the ~100 cell pre-implantation embryo. Despite the vast size range across cell types, cells of a given type are typically uniform in size because cells accurately couple cell growth to division. While some genes affecting cell size have been identified, the molecular mechanisms through which cell growth drives cell division had remained elusive. While it was expected that growth would act to increase the activities of the cyclin-dependent kinases (Cdk) known to promote cell division, this is not the case. Rather, we found that cell growth acts in the opposite manner. Cell growth triggers division by diluting proteins that inhibit cell division, Whi5 in yeast, and the retinoblastoma tumor suppressor Rb in human cells. Thus, inhibitor dilution provides one long sought mechanism coupling cell growth to cell division.