Multiple Regulatory Systems Coordinate DNA Replication with Cell Growth in Bacillus subtilis

Murray, Heath; Koh, Alan

doi:10.1371/journal.pgen.1004731

Cited by 45 publications

(68 citation statements)

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“…Moreover, the precise molecular mechanisms of how active DnaA accumulates in response to growth rate remain elusive. While it has been demonstrated that DnaA is the main factor governing replication frequency in E. coli, the situation seems to be slightly different in B. subtilis (Murray & Koh, 2014). Similar to E. coli, a reduction in DnaA abundance delayed DNA replication in fast-growing cells, which is consistent with a requirement for DnaA in driving frequent replication initiation.…”

Section: Coordination Of Dna Replication With Growth Ratementioning

confidence: 85%

Modulation of Bacterial Proliferation as a Survival Strategy

Heinrich

Leslie

Jonas

2015

Advances in Applied Microbiology

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Section: Coordination Of Dna Replication With Growth Ratementioning

confidence: 85%

Modulation of Bacterial Proliferation as a Survival Strategy

Heinrich

Leslie

Jonas

2015

Advances in Applied Microbiology

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“…Recent work shows that specific ribosomal protein genes link cell growth to replication in Bacillus subtilis (60). We observed similar effects since S10 dosage correlated growth rate and oriC -firing frequency (Fig.…”

Section: Discussionmentioning

confidence: 99%

Macromolecular crowding links ribosomal protein gene dosage to growth rate inVibrio cholerae

Soler-Bistué

Aguilar-Pierlé

García-Garcerá

et al. 2019

Preprint

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16 17 18 Text without Abstract, acknowledgments and legends.Abstract: Ribosomal protein (RP) genes locate near the replication origin (oriC) in fast- 27 growing bacteria, which is thought to have been selected as a translation optimization strategy. 28 Relocation of S10-spc-α locus (S10), which codes for most of the RP, to ectopic genomic 29 positions shows that its relative distance to the oriC correlates to a reduction on its dosage, its 30 expression, and bacterial growth rate. Deep-sequencing revealed that S10 relocation altered 31 chromosomal replication dynamics and genome-wide transcription. Such changes increased as 32 a function of oriC-S10 distance. Strikingly, in this work we observed that protein production 33 capacity was independent of S10 position. Since RP constitute a large proportion of cell mass, 34 lower S10 dosage could lead to changes in macromolecular crowding, impacting cell 35 physiology. Accordingly, cytoplasm fluidity was higher in mutants where S10 is most distant 36 from oriC. In hyperosmotic conditions, when crowding differences are minimized, the growth 37 rate and replication dynamics were highly alleviated in these strains. Therefore, on top of its 38 essential function in translation, RP genomic location contributes to sustain optimal 39 macromolecular crowding. This is a novel mechanism coordinating DNA replication with 40 bacterial growth. 41Introduction: 42 Replication, gene expression and segregation are tightly coordinated with the cell cycle to 43 preserve homeostasis (1, 2). Genome structure is a plausible factor contributing to integrate 44 these many simultaneous processes occurring on the same template. The relative simplicity and 45 the increasing amount of available data render bacterial genomes ideal models to study this 46 subject (3-6). 47Bacterial chromosomes are highly variable in their gene content, but highly conserved in terms 48 of the order of core genes in the chromosomes. Replication begins at a sole replication origin 49 (oriC), proceeding bidirectionally along two equally sized replichores until the terminal region 50 (ter). This organizes the genome along an ori-ter axis that interplays with cell physiology (Fig. 51 1a) (4, 5, 7). For instance, essential genes are overrepresented in the replicative leading strand 52 to avoid head-on collisions between the replication and transcription machineries (8). Large 53 inversions occur preferentially symmetrically with respect to the ori-ter axis to avoid the 54 emergence of replichore size imbalance (9, 10). Recent studies indicate that gene order within 55 the chromosome may play a relevant role in harmonizing the genome structure with cell 56 physiology. Remarkably, key genes coding for nucleoid associated proteins, RNA polymerase 57 modulators, topoisomerases and energy production are arranged along the ori-ter axis following 58 the temporal order of their expression during growth phases (11, 12). In addition, recent studies 59 have showcased an increasing number of traits whose expressio...

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“…In the space allotted, we were barely able to scratch the surface of proteins predicted to act in similar ways to coordinate metabolism with regulation of cytoskeletal function or DNA replication (115)(116)(117)(118)(119). Based on the growing number of factors that appear to interact with MreB and/or FtsZ and have a seemingly unrelated enzymatic function, we would like to end with the following speculation: that at least some of the proteins proposed to have moonlighting functions may actually be utilizing interactions with FtsZ and MreB to localize their enzymatic activities to sites in the cell where their substrate is actively metabolized.…”

Section: Discussionmentioning

confidence: 99%

Metabolism Shapes the Cell

Sperber

Herman

2017

J Bacteriol

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More than 5 decades of work support the idea that cell envelope synthesis, including the inward growth of cell division, is tightly coordinated with DNA replication and protein synthesis through central metabolism. Remarkably, no unifying model exists to account for how these fundamentally disparate processes are functionally coupled. Recent studies demonstrate that proteins involved in carbohydrate and nitrogen metabolism can moonlight as direct regulators of cell division, coordinate cell division and DNA replication, and even suppress defects in DNA replication. In this minireview, we focus on studies illustrating the intimate link between metabolism and regulation of peptidoglycan (PG) synthesis during growth and division, and we identify the following three recurring themes. (i) Nutrient availability, not growth rate, is the primary determinant of cell size. (ii) The degree of gluconeogenic flux is likely to have a profound impact on the metabolites available for cell envelope synthesis, so growth medium selection is a critical consideration when designing and interpreting experiments related to morphogenesis. (iii) Perturbations in pathways relying on commonly shared and limiting metabolites, like undecaprenyl phosphate (Und-P), can lead to pleotropic phenotypes in unrelated pathways.KEYWORDS FtsZ, MreB, UDP-glucose, cell division, gluconeogenesis, metabolism, morphogenesis, peptidoglycan, phosphoenolpyruvate, undecaprenyl phosphate T o accurately partition chromosomes and other cell contents during reproduction, cells must possess mechanisms to organize repeated cycles of cell growth, chromosome replication, and division. Eukaryotes orchestrate this coordination using the cell cycle and separate growth, DNA synthesis, and cytokinesis into distinct, temporally sequestered phases. Bacteria, by contrast, simultaneously increase in cell size and replicate DNA before (or concurrently with) cell division. Elucidating the molecular mechanisms prokaryotes employ to achieve spatiotemporal organization of these intertwined yet functionally disparate processes is of considerable interest to scientists seeking to understand bacterial reproduction, and many outstanding questions remain to be answered. For example, how is DNA replication kept in sync with changing growth and division rates? How are cell dimensions maintained or actively rearranged in response to environmental or developmental cues? What signals do cells sense to switch between increasing in cell size and dividing during the cell cycle? Relatedly, how are these signals transduced to activate/deactivate the distinct machineries required for each process?Perhaps one of the biggest mysteries remaining in bacterial cell biology relates to understanding the regulatory cross talk that must occur to integrate central metabolism with macromolecular biosynthesis. Nutrients are converted into stored energy and precursors used to synthesize macromolecules like DNA and peptidoglycan (PG), so it is no surprise that nutrient availability has a profound impac...

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Multiple Regulatory Systems Coordinate DNA Replication with Cell Growth in Bacillus subtilis

Cited by 45 publications

References 45 publications

Modulation of Bacterial Proliferation as a Survival Strategy

Modulation of Bacterial Proliferation as a Survival Strategy

Macromolecular crowding links ribosomal protein gene dosage to growth rate inVibrio cholerae

Metabolism Shapes the Cell

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