Editing Caulobacter crescentus (section)

==Cell cycle==
The ''Caulobacter'' [[cell cycle]] regulatory system controls many modular subsystems that organize the progression of cell growth and reproduction. A [[control system]] constructed using biochemical and genetic logic circuitry organizes the timing of initiation of each of these subsystems. The central feature of the cell cycle regulation is a cyclical genetic circuit—a cell cycle engine—that is centered around the successive interactions of five master regulatory proteins: DnaA, GcrA, CtrA, SciP, and CcrM whose roles were worked out by the laboratories of [[Lucy Shapiro]] and [[Harley McAdams]].<ref>{{cite journal|last=McAdams|first=HH|author2=Shapiro, L|title=System-level design of bacterial cell cycle control|journal=FEBS Letters|date=Dec 17, 2009|volume=583|issue=24|pages=3984–91|pmid=19766635|doi=10.1016/j.febslet.2009.09.030|pmc=2795017}}</ref><ref>{{cite journal|last=Collier|first=J|author2=Shapiro, L|title=Spatial complexity and control of a bacterial cell cycle|journal=Current Opinion in Biotechnology|date=Aug 2007|volume=18|issue=4|pages=333–40|pmid=17709236|doi=10.1016/j.copbio.2007.07.007|pmc=2716793}}</ref><ref>{{cite journal|doi=10.1073/pnas.1014395107|pmid=20956288|pmc=2973855|title=An essential transcription factor, SciP, enhances robustness of Caulobacter cell cycle regulation|journal=Proceedings of the National Academy of Sciences|volume=107|issue=44|pages=18985–990|year=2010|last1=Tan|first1=M. H.|last2=Kozdon|first2=J. B.|last3=Shen|first3=X.|last4=Shapiro|first4=L.|last5=McAdams|first5=H. H.|bibcode=2010PNAS..10718985T|doi-access=free}}</ref>  These five proteins directly control the timing of expression of over 200 genes. The five master regulatory proteins are synthesized and then eliminated from the cell one after the other over the course of the cell cycle. Several additional cell signaling pathways are also essential to the proper functioning of this cell cycle engine. The principal role of these signaling pathways is to ensure reliable production and elimination of the CtrA protein from the cell at just the right times in the cell cycle.

An essential feature of the ''Caulobacter'' cell cycle is that the chromosome is replicated once and only once per cell cycle. This is in contrast to the ''E. coli'' cell cycle where there can be overlapping rounds of chromosome replication simultaneously underway. The opposing roles of the ''Caulobacter'' DnaA and CtrA proteins are essential to the tight control of ''Caulobacter'' chromosome replication.<ref>{{cite journal|last=Collier|first=J |author2=Murray, SR |author3=Shapiro, L|title=DnaA couples DNA replication and the expression of two cell cycle master regulators|journal=The EMBO Journal|date=Jan 25, 2006|volume=25|issue=2|pages=346–56|pmid=16395331|doi=10.1038/sj.emboj.7600927|pmc=1383511}}</ref>  The DnaA protein acts at the [[origin of replication]] to initiate the replication of the chromosome. The CtrA protein, in contrast, acts to block initiation of replication, so it must be removed from the cell before chromosome replication can begin. Multiple additional regulatory pathways integral to cell cycle regulation and involving both phospho signaling pathways and regulated control of protein proteolysis<ref>{{cite journal|last=Jenal|first=U|title=The role of proteolysis in the ''Caulobacter crescentus'' cell cycle and development|journal=Research in Microbiology|date=Nov 2009|volume=160|issue=9|pages=687–95|pmid=19781638|doi=10.1016/j.resmic.2009.09.006|doi-access=free}}</ref>  act to assure that DnaA and CtrA are present in the cell just exactly when needed.

Each process activated by the proteins of the cell cycle engine involve a cascade of many reactions. The longest subsystem cascade is DNA replication. In ''Caulobacter'' cells, replication of the chromosome involves about 2 million DNA synthesis reactions for each arm of the chromosome over 40 to 80 min depending on conditions. While the average time for each individual synthesis reaction can be estimated from the observed average total time to replicate the chromosome, the actual reaction time for each reaction varies widely around the average rate. This leads to a significant and inevitable cell-to-cell variation time to complete replication of the chromosome. There is similar random variation in the rates of progression of all the other subsystem reaction cascades.  The net effect is that the time to complete the cell cycle varies widely over the cells in a population even when they all are growing in identical environmental conditions. Cell cycle regulation includes [[feedback]] signals that pace progression of the cell cycle engine to match progress of events at the regulatory subsystem level in each particular cell. This control system organization, with a controller (the cell cycle engine) driving a complex system, with modulation by feedback signals from the controlled system creates a closed loop control system.

The rate of progression of the cell cycle is further adjusted by additional signals arising from cellular sensors that monitor environmental conditions (for example, nutrient levels and the oxygen level) or the internal cell status (for example, presence of DNA damage).<ref>{{cite journal|last=Shen|first=X|author2=Collier, J|author3=Dill, D|author4=Shapiro, L|author5=Horowitz, M|author6=McAdams, HH|title=Architecture and inherent robustness of a bacterial cell-cycle control system|journal=Proceedings of the National Academy of Sciences of the United States of America|date=Aug 12, 2008|volume=105|issue=32|pages=11340–45|pmid=18685108|doi=10.1073/pnas.0805258105|pmc=2516238|bibcode=2008PNAS..10511340S|doi-access=free}}</ref>