期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：52
页码：15000-15005
DOI：10.1073/pnas.1617932114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceHow bacteria regulate cell division to achieve cell size homeostasis, with concomitant coordination of DNA replication, is a fundamental question. Currently, there exist several competing models for cell cycle regulation in Escherichia coli. We performed experiments where we systematically perturbed cell dimensions and found that average cell volume scales exponentially with the product of the growth rate and the time from initiation of DNA replication to the corresponding cell division. Our data support a model in which cells initiate replication on average at a constant volume per origin and divide a constant time thereafter. 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 Schaechters 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.
关键词：cell cycle ; cell growth ; E. coli ; DNA replication ; cell dimension
