Each transcriptional wave from a yeast cell cycle promoter lasts 20–25 min; so stringing together 3 or 4 of them should allow the construction of a simple 90-min cell cycle. But, says van Oudenaarden, “if you didn't optimize the system, the cell cycle waves get washed out very easily. Within a quarter or a third of a 90-minute cycle, the waves are almost completely gone.”
Rather than investigating every last detail of real cell cycle oscillators, the MIT group built, both in yeast cells and in silico, a simple circuit that transmits cell cycle–like oscillations. They found that a slow process such as transcription (and the lengthy persistence of the resulting mRNA) led to a loss of the initial periodicity information from a cell cycle promoter.
A faster process, such as accelerated nuclear import, gave a shorter delay but maintained the high peak-to-trough information of the original oscillation. Stringing together a series of such fast processes, such as protein modifications, should give accurate oscillations of approximately the correct duration. The high peak-to-trough ratio can also be restored with feedback loops and nonlinear activation and degradation steps. All of these tricks were known to exist in the cell cycle, but the MIT group has now established why they are necessary. ▪