The DnaA Tale

Hansen, Flemming; Atlung, Tove

doi:10.3389/fmicb.2018.00319

Cited by 66 publications

(135 citation statements)

References 181 publications

(271 reference statements)

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…DnaA is a widely conserved essential protein required for initiation of DNA replication in bacteria. In bacteria in which it has been examined, replication initiation depends in part on accumulation of a sufficient number of DnaA molecules at the origin of replication [39][40][41]. Previous studies and our data showed that an underexpression of dnaA causes an initiation delay, whereas an overexpression of dnaA causes premature initiation (Fig.…”

Section: Dynamic Perturbation Of Replication Initiator Synthesis To Tsupporting

confidence: 62%

Mechanistic origin of cell-size control and homeostasis in bacteria

Treut

Sauls

et al. 2018

Preprint

View full text Add to dashboard Cite

HIGHLIGHTS• The adder requires accumulation of division proteins to a threshold for division.• The adder requires constant production of division proteins during cell elongation.• In E. coli and B. subtilis, initiation and division are independently controlled. • In E. coli and B. subtilis, cell division exclusively drives size homeostasis. GRAPHICAL ABSTRACT eTOC Blurb Si and Le Treut et al. show that cell-size homeostasis in bacteria is exclusively driven by accumulation of division proteins to a threshold and their balanced biosynthesis during cell elongation. This mechanistic insight allowed them to reprogram cell-size homeostasis in both E. coli and B. subtilis. Evolutionary implications are discussed.ABSTRACT Evolutionarily divergent bacteria share a common phenomenological strategy for cell-size homeostasis under steady-state conditions. In the presence of inherent physiological stochasticity, cells following this "adder" principle gradually return to their steady-state size by adding a constant volume between birth and division regardless of their size at birth. However, the mechanism of the adder has been unknown despite intense efforts. In this work, we show that the adder is a direct consequence of two general processes in biology: (1) threshold --accumulation of initiators and precursors required for cell division to a respective fixed number, and (2) balanced biosynthesis -maintenance of their production proportional to volume growth. This mechanism is naturally robust to static growth inhibition, but also allows us to "reprogram" cell-size homeostasis in a quantitatively predictive manner in both Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. By generating dynamic oscillations in the concentration of the division protein FtsZ, we were able to oscillate cell size at division and systematically break the adder. In contrast, periodic induction of replication initiator protein DnaA caused oscillations in cell size at initiation, but did not alter division size or the adder. Finally, we were able to restore the adder phenotype in slow-growing E. coli, the only known steady-state growth condition wherein E. coli significantly deviates from the adder, by repressing active degradation of division proteins. Together these results show that cell division and replication initiation are independently controlled at the gene-expression level, and that division processes exclusively drive cell-size homeostasis in bacteria.labeled replisome protein (DnaN-YPet) to image replication cycles, and a microfluidic mother machine to follow continuous lineages during steady-state growth [3, 26] (Fig. 1A, Fig. S1; STAR Methods).A major technical challenge arises in studying replication dynamics when two replisome foci spatially overlap, which makes it difficult to analyze overlapping replication cycles. To resolve this issue, we tracked multiple replication forks from initiation to termination by extending previous imaging methods [8, 19,27,28] using the "intensity weighting" techniques [29,30] develo...

show abstract

Section: Dynamic Perturbation Of Replication Initiator Synthesis To Tsupporting

confidence: 62%

Mechanistic origin of cell-size control and homeostasis in bacteria

Treut

Sauls

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…This function has long been known to be ATP-dependent. Yet the role of ATP is poorly understood (Hansen and Atlung, 2018). The function of AAA+ superfamily proteins is, indeed, generally interpreted as mechanical (Snider et al, 2008).…”

Section: Other Processes Working Out Specific Features Of Nucleic Acidsmentioning

confidence: 99%

Omnipresent Maxwell's demons orchestrate information management in living cells

Boël

Danot

Lorenzo

et al. 2019

Microbial Biotechnology

View full text Add to dashboard Cite

Summary The development of synthetic biology calls for accurate understanding of the critical functions that allow construction and operation of a living cell. Besides coding for ubiquitous structures, minimal genomes encode a wealth of functions that dissipate energy in an unanticipated way. Analysis of these functions shows that they are meant to manage information under conditions when discrimination of substrates in a noisy background is preferred over a simple recognition process. We show here that many of these functions, including transporters and the ribosome construction machinery, behave as would behave a material implementation of the information‐managing agent theorized by Maxwell almost 150 years ago and commonly known as Maxwell's demon (MxD). A core gene set encoding these functions belongs to the minimal genome required to allow the construction of an autonomous cell. These MxDs allow the cell to perform computations in an energy‐efficient way that is vastly better than our contemporary computers.

show abstract

“…Three high affinity DnaA binding sites (R1, R2, R4) present in the oriC sequence are occupied throughout most of the cell cycle, and both DnaA-ADP and DnaA-ATP can interact with them. However, only DnaA-ATP can bind several low-affinity sites, forming two oppositely arrays between R1-R2 and R2-R4 DnaA-boxes (Hansen & Atlung, 2018).…”

Section: Dna Replicationmentioning

confidence: 99%

When size matters – coordination of growth and cell cycle in bacteria

2019

View full text Add to dashboard Cite

Bacterial cells often inhabit environments where conditions can change rapidly. Therefore, a lot of bacterial species developed control strategies allowing them to grow and divide very fast during feast and slow down both parameters during famine. Under rich nutritional conditions, fast-growing bacteria can divide with time interval equal to half of the period required to synthesize their chromosomes. This is possible due to multifork replication which allows ancestor cells to start copying genetic material for their descendants. This reproduction scheme was most likely selected for, since it enables maximization of growth rate and hence – effective competition for resources, while ensuring that DNA replication will not become limiting for cell division. Even with this complexity of cell cycle, isogenic bacterial cells grown under defined conditions display remarkably narrow distribution of sizes. This may suggest that mechanisms exists to control cell size at division step. Alternative view, with great support in experimental data is that the only step coordinated with cell growth is the initiation of DNA replication. Despite decades of research we are still not sure what the driving forces in bacterial cell cycle are. In this work we review recent advances in understanding coordination of growth with DNA replication coming from single cell studies and systems biology approaches.

show abstract

The DnaA Tale

Cited by 66 publications

References 181 publications

Mechanistic origin of cell-size control and homeostasis in bacteria

Mechanistic origin of cell-size control and homeostasis in bacteria

Omnipresent Maxwell's demons orchestrate information management in living cells

When size matters – coordination of growth and cell cycle in bacteria

Contact Info

Product

Resources

About