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Oscillating Global Regulators Control the Genetic Circuit Driving a Bacterial Cell Cycle
Julia Holtzendorff,1Dean Hung,1Peter Brende,2Ann Reisenauer,1Patrick H. Viollier,1Harley H. McAdams,1Lucy Shapiro1*
A newly identified cell-cycle master regulator protein, GcrA,together with the CtrA master regulator, are key componentsof a genetic circuit that drives cell-cycle progression andasymmetric polar morphogenesis in Caulobacter crescentus. Thecircuit drives out-of-phase temporal and spatial oscillationof GcrA and CtrA concentrations, producing time- and space-dependenttranscriptional regulation of modular functions that implementcell-cycle processes. The CtrA/GcrA regulatory circuit controlsexpression of polar differentiation factors and the timing ofDNA replication. CtrA functions as a silencer of the replicationorigin and GcrA as an activator of components of the replisomeand the segregation machinery.
1 Department of Developmental Biology, School of Medicine, Beckman Center, Stanford University, Stanford, CA 94305, USA. 2 Department of Electrical Engineering, School of Engineering, Stanford University, Stanford, CA 94305, USA.
* To whom correspondence should be addressed. E-mail: shapiro{at}stanford.edu
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