New work from Holstege and colleagues reveals that 'resting phase' is something of a misnomer. Their results in Saccharomyces cerevisiae show that many genes are actively transcribed during this time and that, contrary to the current view, RNA polymerase II remains associated with DNA, poised for transcription on exit from the resting phase.

The authors used nutrient-starved S. cerevisiae as a model for the resting phase of the eukaryotic cell cycle. Over a period of 9 days, they carried out poly(A) RNA dot-blot hybridization and microarray analysis to look at gene expression during the stationary phase — the yeast equivalent of resting phase — in a single experiment. Previous work indicated that a general shutdown of transcription occurs at this stage of the cell cycle. Unexpectedly, the authors saw that although most transcription does stop, several transcripts become upregulated specifically during the stationary phase.

The dynamics of transcription in the stationary phase is not simple; for example, the authors saw three peaks of RNA accumulation. They also showed that exit from the stationary phase is followed by a strikingly rapid burst of transcription. Prompted by this observation, and the fact that even in the stationary phase genes can become activated in response to environmental changes, the authors used genome-wide chromatin immunoprecipitation to show that RNA polymerase II predominantly resides in intergenic regions, upstream of open reading frames. This contrasts with the current view that the polymerase needs to be recruited to DNA on activation.

Understanding the resting phase, and how a cell might switch from this state to undergo cell division, has important implications, for example, in cancer and ageing. This work prompts us to re-examine our thinking about the so-called quiescent phase of the cell cycle and about the regulation of gene transcription. Importantly, it also paves the way for future, more detailed studies of what really happens in the nucleus during what is the longest stage of a cell's life.