title: Interrogating the Escherichia coli cell cycle by cell dimension perturbations.
abstract: Bacteria tightly regulate and coordinate the various events in their cell cycles to duplicate themselves accurately and to control their cell sizes. Growth of Escherichia coli, in particular, follows a relation known as Schaechter's growth law. This law says that the average cell volume scales exponentially with growth rate, with a scaling exponent equal to the time from initiation of a round of DNA replication to the cell division at which the corresponding sister chromosomes segregate. Here, we sought to test the robustness of the growth law to systematic perturbations in cell dimensions achieved by varying the expression levels of mreB and ftsZ We found that decreasing the mreB level resulted in increased cell width, with little change in cell length, whereas decreasing the ftsZ level resulted in increased cell length. Furthermore, the time from replication termination to cell division increased with the perturbed dimension in both cases. Moreover, the growth law remained valid over a range of growth conditions and dimension perturbations. The growth law can be quantitatively interpreted as a consequence of a tight coupling of cell division to replication initiation. Thus, its robustness to perturbations in cell dimensions strongly supports models in which the timing of replication initiation governs that of cell division, and cell volume is the key phenomenological variable governing the timing of replication initiation. These conclusions are discussed in the context of our recently proposed "adder-per-origin" model, in which cells add a constant volume per origin between initiations and divide a constant time after initiation.
authors.affiliation: Center for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.|University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zheng
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
authors.forename: Po-Yi
authors.initials: PY
authors.lastname: Ho
authors.affiliation: Center for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Tang
authors.affiliation: Center for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.|University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors.forename: Weirong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Center for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: Dengjin
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Kleckner
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; cl.liu@siat.ac.cn arielamir@seas.harvard.edu.
authors.forename: Ariel
authors.initials: A
authors.lastname: Amir
authors.affiliation: Center for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People's Republic of China; cl.liu@siat.ac.cn arielamir@seas.harvard.edu.|University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
authors.forename: Chenli
authors.initials: C
authors.lastname: Liu
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D002473:Cell Wall / Q000378:metabolism; D002876:Chromosomes, Bacterial; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004261:DNA Replication; D004269:DNA, Bacterial / Q000096:biosynthesis; D004926:Escherichia coli / Q000166:cytology* / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000378:metabolism; D010957:Plasmids
chemical_list: D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C071525:FtsZ protein, Bacteria; C078473:MreB protein, E coli
keywords: DNA replication; E. coli; cell cycle; cell dimension; cell growth