Successive waves of transcriptional repression and de-repression license cell cycle progression in an archaeon

Archaea of the order Sulfolobales execute a well-structured cell cycle program similar to that of eukaryotic cells. Here, we show that three ribbon-helix-helix domain transcription factors, aCcr1, aCcr2, and aCcr3, play pivotal roles in controlling the cell cycle progression in the thermoacidophilic archaeon Saccharolobus islandicus by licensing the timely transcription of the key genes that define the cell cycle phases. The three transcription factors act as repressors and recognize similar regulatory sequences. However, their expression timing during the cell cycle differs. The disengagement of aCcr2 from the recognized promoters prior to the M phase appears to be controlled through its phosphorylation by the cyclically-expressed eukaryotic-like kinase aCcrK (ePK2). The synergy between aCcr1, aCcr2, and aCcr3 is also achieved through their differential affinities for the promoters and the levels of protein expression. The global regulation of the Sulfolobales cell cycle may be achieved not through transcriptional activation, but rather by repression of the key genes during strategic moments of the cell cycle. We propose a phosphorylation-assisted braking-point model for the cell cycle control in Sulfolobales, which may represent a simple evolutionary intermediate on the way to the more complex cell cycle regulation in eukaryotes.