Resumption of cell proliferation from stationary Phase

All living cells are capable of ceasing cell proliferation and entering a non-proliferating or quiescent state, commonly referred to as G0 or (in the case of microbial cultures) stationary phase. We know little about the regulation of the transition between quiescence and active cell proliferation, but the transition undoubtedly requires the reprogramming of regulatory networks made up of signal transduction pathways, remodeling of cellular structures and processes, and altered physiology. Indeed, the overwhelming majority of cell biology studies on eukaryotic cells has concentrated on the proliferating cell, even though most microorganisms in the wild are in stationary phase most of the time, and most cells in metazoan organisms are also in stationary phase (or G0) for long periods of time. For example, nearly all neurons are in stationary phase from the moment they terminally differentiate for the remaining life of the organism. Many cancers cannot start until the cell that becomes cancerous exits from the quiescent state and resumes the proliferative cell cycle: brain cancers are but one example. Using the genetic and molecular facility of the yeast, Saccharomyces cerevisiae, we intend to identify proteins that play a specific role in the resumption of cell proliferation from stationary phase. Findings with yeast are generally applicable to all cells, including humans, so that understanding the biology of stationary phase will undoubtedly shed light on G0 in higher cells, an understanding that will be important for human health as well as for basic knowledge of the behavior of all eukaryotes.