Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus

Summary Cell cycle transitions are often triggered by the proteolysis of key regulatory proteins. In C aulobacter crescentus , the G 1‐ S transition involves the degradation of an essential DNA ‐binding response regulator, CtrA , by the ClpXP protease. Here, we show that another critical cell cycle regulator, SciP , is also degraded during the G 1‐ S transition, but by the L on protease. SciP is a small protein that binds directly to CtrA and prevents it from activating target genes during G 1. We demonstrate that SciP must be degraded during the G 1‐ S transition so that cells can properly activate CtrA ‐dependent genes following DNA replication initiation and the reaccumulation of CtrA . These results indicate that like CtrA , SciP levels are tightly regulated during the C aulobacter cell cycle. In addition, we show that formation of a complex between CtrA and SciP at target promoters protects both proteins from their respective proteases. Degradation of either protein thus helps trigger the destruction of the other, facilitating a cooperative disassembly of the complex. Collectively, our results indicate that ClpXP and Lon each degrade an important cell cycle regulator, helping to trigger the onset of S phase and prepare cells for the subsequent programmes of gene expression critical to polar morphogenesis and cell division.