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Description :
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Combined CtrA and GcrA Transcriptional Network Creates Engine that Drives the Cell Cycle Forward. A complex oscillatory genetic circuit controls Caulobacter crescentus cell-cycle progression and asymmetric polar cell-cycle progression and asymmetric polar morphogenesis. Two tightly regulated master regulatory proteins, CtrA and GcrA, recently were shown to form the core oscillator.1 Their intracellular concentrations activate or repress numerous cell cycle–regulated genes. Many of these genes are themselves top-level regulators of modular functions that execute the functions involved in cell-cycle progression (e.g., chromosome replication). Recent results elaborating this circuit include characterization of the regulons of two additional key Caulobacter cell-cycle regulatory proteins (publications in preparation). Genetic Regulation in Bacteria Progression through the cell cycle requires precise coordination of DNA replication, chromosome segregation, cell division, and cell growth. Study of the aquatic bacterium Caulobacter crescentus has shown that a small number of “master regulator” genes and their proteins provide this control. These proteins (CtrA and GcrA on the left side of the figure) interact with each other to form top-level regulatory circuitry that produces both temporal and spatial oscillations in their intracellular concentrations.1 Changing concentrations of these regulatory proteins activate or repress key genes to initiate modular functions that implement the cell cycle through such activities as chromosome replication, cytokinesis, and the timing of construction and destruction of polar organelles. The general features of the top-level genetic circuits comprising the cell’s control system are emerging. The control system is hierarchical, modular, and asynchronous. Genes are expressed “just in time”—that is, only when their protein products are needed to perform their function—and then quickly degraded. The number of master regulator proteins is relatively small, and their expression and proteolysis are very tightly controlled. Environmental and cell status signals also tend to flow through master regulators. The set of master regulators tends to be conserved as a system in related bacterial species, but the set of controlled genes is less conserved.2 Bacterial species’ fitness strategies are embodied in their master regulator genetic circuitry. The function of bacterial cells, and indeed all cells, is very machinelike, with every cell’s processes for growth, division, and responses to internal and external signals tightly and predictably controlled by the embedded biochemical and genetic logic circuits. [Harley McAdams, Stanford University]
References
1. J. Holtzendorff et al.,
“Oscillating Global Regulators Control the Genetic Circuit Driving
a Bacterial Cell Cycle,” Science 304,
983–7 (2004).
2. H. H. McAdams, B. Srinivasan, and A. P. Arkin,
“The Evolution of Genetic Regulatory Systems in Bacteria,” Nat.
Rev. Genet. 58, 169–78 (2004). |
