Initiation of chromosome replication controls both division and replication cycles in E. coli through a double-adder mechanism
Authors: Erik van Nimwegen
Guillaume Witz
Thomas Julou
Journal: eLife (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: E. coli; adder; bacterial cell division; cell cycle; computational biology
Affiliations: Biozentrum, University of Basel, Basel, Switzerland., Swiss Institute of Bioinformatics, University of Bern, Bern, Switzerland.

Abstract:  Living cells proliferate by completing and coordinating two cycles, a division cycle controlling cell size and a DNA replication cycle controlling the number of chromosomal copies. It remains unclear how bacteria such as Escherichia coli tightly coordinate those two cycles across a wide range of growth conditions. Here, we used time-lapse microscopy in combination with microfluidics to measure growth, division and replication in single E. coli cells in both slow and fast growth conditions. To compare different phenomenological cell cycle models, we introduce a statistical framework assessing their ability to capture the correlation structure observed in the data. In combination with stochastic simulations, our data indicate that the cell cycle is driven from one initiation event to the next rather than from birth to division and is controlled by two adder mechanisms: the added volume since the last initiation event determines the timing of both the next division and replication initiation events. 

Retracted: No

PubPeer comments:
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 Dear Elliptacalles Baeticus, Thank you for bringing our attention to this figure and your strife for scientific rigor. We would like to clarify a few points: 1. The manuscript was eventually rejected from the Cells journal. Therefore Journal of Proteomics publication (10.1016 j.jprot.2020.103682) is the first instance of the peer-reviewed release of these results. The RNA seq data in the way it was presented in the Cells preprint (10.20944 preprints201907.0140.v1) was not released so far as part peer-review publication. In Journal of Proteomics, we did provide the reference to the preprint as reference [24] u201cH.S. Huang, S. Madhu, A. Lennikov, A. Mukwaya, L. Fan, Pathway-focused gene interaction analysis reveals the regulation of TGF-beta, pentose phosphate and antioxidant defense system by placental growth factor in retinal endothelial cell functions: implication in diabetic retinopathy, Preprints (2019) 1u201324, https: doi. org 10.20944 preprints201907.0140.v1.u201d referring to the RNA seq data analysis. Please note, preprints are not peer-reviewed and frequently contain early versions of the results and text that are subject to the significant change during the submission revision process. 2. Part of the criticism from the Cells rejection was the confusing WB result that includes rhPlGF as we have conducted the proteomics analysis (and RNA seq) for Control and PlGF antibody conditions, but not rhPlGF treated conditions in HREC. Therefore, we have removed rhPlGF data from the ECIS assay and the blot for the sake of narrative flow and to avoid readership confusion. There is no effect of rhPlGF data removal from the blot to the study results in discussion or conclusions. The proteomics data is also consistent with the WB findings. The increase in G6PD and barrier function proteins by PlGF inhibition in the endothelial cells are robust, reproducible phenomena. You can refer to our recent publication in FASEBJ u201cPlacental growth factor negatively regulates retinal endothelial cell barrier function through suppression of glucose-6-phosphate dehydrogenase and antioxidant defense systemsu201d (doi.org 10.1096 fj.201901353R) were in same experimental conditions including G6PD and barrier function proteins upregulation induced by PlGF inhibition as well as itu2019s decrease induced by rhPlGF that are explored in much greater detail by several scientific techniques in multiple samples. We will be happy to respond to further specific criticism if you would like to provide it. Sincerely, Hu Huang, Ph.D. ,