Regulation of the bacterial cell cycle by an integrated genetic circuit

Nature 2006 Dec 14; 444(7121): 899-904

Abstract

How bacteria regulate its cell cycle at molecule level is poorly understood. Caulobacter crescentus is an attractive cell cycle model because its cell cycle can be easily distinguished. The cell cycle in C. crescentus can be divided into G1, S, and G2 phases, as in eukaryocyte. Two component response regulator, CtrA, is the master transcription factor for cell cycle regulation. In G1 phase,CtrA is phosphorylated and can block the origin of replication. At the G1-S transition, CtrA is dephosphorylated and degraded, and thus DNA replication can be started. Other components also play an important role on cell cycle regulation. For example, histidine kinase CckA is required for CtrA phosphorylation and the phenotype on response regulator DivK mutant is similar to CtrAconstitutively-activated strain. Although many components related to cell cycle regulation have been identified, the connection among those components is still uncharacterized. In this paper, authors identify an essential gene, ChpT, a histidine phosphotransferase, by bioinformatics approach. Genetic and biochemical analysis suggested that CckA can initiate two phosphorylays, which will go through ChpT, and in turn phosphorylates and stabilizes CtrA. DivK is also known to control these two processes on CtrA. By using cell biological assay and genetic approach, they found that DivK can dephosphorylate and delocalize CckA, resulting in CtrA inactivation. The transcription of divK can be enhanced by phosphorylated CtrA, and phosphorylated DivK can block the activation of CckA, which is the upstream signal of CtrA. Thus it forms a negative feedback loop from CtrA inducing divK to DivK blocking CtrA, via CckA. This negative feedback loop can account for CtrA oscillating. Combining the other components and connection which they identified, this single genetic circuit can build up the underline mechanism of the cell cycle in C.crescentus.

References

1.   Biondi, E. G., S. J. Reisinger, J. M. Skerker, M. Arif, B. S. Perchuk, K. R. Ryan, and M. T. Laub. 2006. Regulation of the bacterial cell cycle by an integrated genetic circuit. Nature444:899-904.

2.   McAdams, H. H., and L. Shapiro. 2003. A bacterial cell-cycle regulatory network operating in time and space. Science 301:1874-7.