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Science 304 (5673): 983-987

Copyright © 2004 by the American Association for the Advancement of Science

Oscillating Global Regulators Control the Genetic Circuit Driving a Bacterial Cell Cycle

Julia Holtzendorff,1 Dean Hung,1 Peter Brende,2 Ann Reisenauer,1 Patrick H. Viollier,1 Harley H. McAdams,1 Lucy Shapiro1*

Abstract: A newly identified cell-cycle master regulator protein, GcrA, together with the CtrA master regulator, are key components of a genetic circuit that drives cell-cycle progression and asymmetric polar morphogenesis in Caulobacter crescentus. The circuit drives out-of-phase temporal and spatial oscillation of GcrA and CtrA concentrations, producing time- and space-dependent transcriptional regulation of modular functions that implement cell-cycle processes. The CtrA/GcrA regulatory circuit controls expression of polar differentiation factors and the timing of DNA replication. CtrA functions as a silencer of the replication origin and GcrA as an activator of components of the replisome and 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}

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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