Three transcription factors coordinate the archaeal cell cycle progression through a regulatory braking point mechanism
Archaea of the order Sulfolobales execute a well-structured cell cycle program similar to that of eukaryotic cells. However, unlike eukaryotes, archaea lack cyclins and cyclin-dependent kinases and thus the mechanism of cell cycle regulation remained enigmatic. Here, we show that three essential ribbon-helix-helix domain transcription factors, namely, aCcr1, aCcr2, and aCcr3, play pivotal roles in controlling the cell cycle progression in the thermoacidophilic archaeon Saccharolobus islandicus. Coordinated expression of aCcr1 during M-G1 phase, aCcr3 during G1-S phase, and aCcr2 throughout the cell cycle ensures the timely transcription of the key genes that define the cell cycle phases. These include genes involved in chromosome dimer resolution, chromosome segregation, cell division, chromatin organization, DNA replication and repair, protein phosphorylation and degradation and metabolisms of amino acids, tRNA and carbohydrates. The synergy between aCcr1, aCcr2, and aCcr3 is achieved through their differencial affinities for the promoters and the levels of protein expression. We propose that 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 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.