ArticleNature communications2022
Robust replication initiation from coupled homeostatic mechanisms.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Devising a divisome for synthetic cells.Nature reviews. Chemistry · 2026Review
- Review
- The chromosomal origin of replication as the basis for the spatio-temporal biology of bacteria.Frontiers in microbiology · 2026Review
- Extrusion-modulated DnaA activity oscillations coordinate DNA replication with biomass growth.eLife · 2025Article
- The Escherichia coli replication initiator DnaA is titrated on the chromosome.Nature communications · 2025Article
- The design of unit cells by combining the self-reproduction systems and metabolic cushioning loads.Communications biology · 2025Article
- Relative Distribution of DnaA and DNA inInternational journal of molecular sciences · 2025Article
- Spatio-temporal organization of theEcoSal Plus · 2024Review
- Dispensability of extrinsic DnaA regulators inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Direct single-cell observation of a keyScience advances · 2024Article
- Mechanisms of cell size regulation in slow-growing Escherichia coli cells: discriminating models beyond the adder.NPJ systems biology and applications · 2024Article
- Cell cycle-coordinated maintenance of theEcoSal Plus · 2023Review
- Open Questions about the Roles of DnaA, Related Proteins, and Hyperstructure Dynamics in the Cell Cycle.Life (Basel, Switzerland) · 2023Review
- Regulatory elements coordinating initiation of chromosome replication to theProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Recollections of a Helmstetter Disciple.Life (Basel, Switzerland) · 2023Review
- Using conditional independence tests to elucidate causal links in cell cycle regulation inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Gene expression model inference from snapshot RNA data using Bayesian non-parametrics.Nature computational science · 2023Article
- Robust replication initiation from coupled homeostatic mechanisms.Nature communications · 2022Article
- Article
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Authors and funding
2 authors.
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Abstract
The bacterium Escherichia coli initiates replication once per cell cycle at a precise volume per origin and adds an on average constant volume between successive initiation events, independent of the initiation size. Yet, a molecular model that can explain these observations has been lacking. Experiments indicate that E. coli controls replication initiation via titration and activation of the initiator protein DnaA. Here, we study by mathematical modelling how these two mechanisms interact to generate robust replication-initiation cycles. We first show that a mechanism solely based on titration generates stable replication cycles at low growth rates, but inevitably causes premature reinitiation events at higher growth rates. In this regime, the DnaA activation switch becomes essential for stable replication initiation. Conversely, while the activation switch alone yields robust rhythms at high growth rates, titration can strongly enhance the stability of the switch at low growth rates. Our analysis thus predicts that both mechanisms together drive robust replication cycles at all growth rates. In addition, it reveals how an origin-density sensor yields adder correlations.
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