Project description:Archaea of the order Sulfolobales execute a well-structured cell cycle program similar to that of eukaryotic cells. However, the mechanism of cell cycle regulation remains enigmatic. Here, we show that three essential 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: aCcr1 is expressed immediately after the cell division, aCcr3 during the transition between the G1 and genome replication (S) phase, whereas aCcr2 is expressed throughout the cell cycle. The disengagement of aCcr2 from the recognized promoters prior to the M phase is controlled through its phosphorylation by the cyclically-expressed eukaryotic-like kinase aCcrK (archaea cell cycle regulatory kinase). 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.
Project description:Archaea of the order Sulfolobales execute a well-structured cell cycle program similar to that of eukaryotic cells. However, the mechanism of cell cycle regulation remains enigmatic. Here, we show that three essential 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: aCcr1 is expressed immediately after the cell division, aCcr3 during the transition between the G1 and genome replication (S) phase, whereas aCcr2 is expressed throughout the cell cycle. The disengagement of aCcr2 from the recognized promoters prior to the M phase is controlled through its phosphorylation by the cyclically-expressed eukaryotic-like kinase aCcrK (archaea cell cycle regulatory kinase). 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.