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  • Review Article
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The bacterial cell cycle, chromosome inheritance and cell growth

Abstract

All viable bacterial cells, whether they divide symmetrically or asymmetrically, must coordinate their growth, division, cell volume and shape with the inheritance of the genome. These coordinated processes maintain genome integrity over generations as chromosomes are duplicated and segregated during each cell cycle, and include the organization of DNA into nucleoids, controlled and faithful DNA replication, chromosome unlinking and faithful segregation into daughter cells. In this Review, we explore the contributions of chromosome structure and nucleoid organization to cell cycle regulation, detail the cellular processes involved in the initiation of DNA replication and DNA segregation and explore how those processes are linked to cell growth and cell division. Furthermore, we address how the study of a growing number of bacterial species enables the search for common principles that underlie the coordination of chromosome inheritance with the cell cycle.

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Fig. 1: Stages of the cell cycle in relation to growth rate.
Fig. 2: Organization of the chromosome and nucleoid.
Fig. 3: Control of initiation of DNA replication.
Fig. 4: Regulation of the rate of synthesis of DNA.

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References

  1. Willis, L. & Huang, K. C. Sizing up the bacterial cell cycle. Nat. Rev. Microbiol. 15, 606–620 (2017).

    CAS  PubMed  Google Scholar 

  2. Schneiker, S. et al. Complete genome sequence of the myxobacterium Sorangium cellulosum. Nat. Biotechnol. 25, 1281–1289 (2007).

    CAS  PubMed  Google Scholar 

  3. Han, K. et al. Extraordinary expansion of a Sorangium cellulosum genome from an alkaline milieu. Sci. Rep. 3, 2101 (2013).

    PubMed  PubMed Central  Google Scholar 

  4. Bennett, G. M. & Moran, N. A. Small, smaller, smallest: the origins and evolution of ancient dual symbioses in a phloem-feeding insect. Genome Biol. Evol. 5, 1675–1688 (2013).

    PubMed  PubMed Central  Google Scholar 

  5. Jun, S. Chromosome, cell cycle, and entropy. Biophys. J. 108, 785–786 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Stracy, M. et al. Live-cell superresolution microscopy reveals the organization of RNA polymerase in the bacterial nucleoid. Proc. Natl Acad. Sci. USA 112, E4390–E4399 (2015).

    CAS  PubMed  Google Scholar 

  7. Reyes-Lamothe, R., Nicolas, E. & Sherratt, D. J. Chromosome replication and segregation in bacteria. Annu. Rev. Genet. 46, 121–143 (2012).

    CAS  PubMed  Google Scholar 

  8. Wang, X., Montero Llopis, P. & Rudner, D. Z. Bacillus subtilis chromosome organization oscillates between two distinct patterns. Proc. Natl Acad. Sci. USA 111, 12877–12882 (2014).

    CAS  PubMed  Google Scholar 

  9. Badrinarayanan, A., Le, T. B. & Laub, M. T. Bacterial chromosome organization and segregation. Annu. Rev. Cell Dev. Biol. 31, 171–199 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. den Blaauwen, T. Prokaryotic cell division: flexible and diverse. Curr. Opin. Microbiol. 16, 738–744 (2013).

    Google Scholar 

  11. Sauls, J. T., Li, D. & Jun, S. Adder and a coarse-grained approach to cell size homeostasis in bacteria. Curr. Opin. Cell Biol. 38, 38–44 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Schaechter, M., Bentzon, M. W. & Maaloe, O. Synthesis of deoxyribonucleic acid during the division cycle of bacteria. Nature 183, 1207–1208 (1959).

    CAS  PubMed  Google Scholar 

  13. Cooper, S. & Helmstetter, C. E. Chromosome replication and the division cycle of Escherichia coli B/r. J. Mol. Biol. 31, 519–540 (1968).

    CAS  PubMed  Google Scholar 

  14. Donachie, W. D. Relationship between cell size and time of initiation of DNA replication. Nature 219, 1077–1079 (1968).

    CAS  PubMed  Google Scholar 

  15. Dubarry, N., Willis, C. R., Ball, G., Lesterlin, C. & Armitage, J. P. In vivo imaging of the segregation of the 2 chromosomes and the cell division proteins of Rhodobacter sphaeroides reveals an unexpected role for MipZ. mBio 10, e02515-18 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Collier, J. Regulation of chromosomal replication in Caulobacter crescentus. Plasmid 67, 76–87 (2012).

    CAS  PubMed  Google Scholar 

  17. Helmstetter, C., Cooper, S., Pierucci, O. & Revelas, E. On the bacterial life sequence. Cold Spring Harb. Symp. Quant. Biol. 33, 809–822 (1968).

    CAS  PubMed  Google Scholar 

  18. Stokke, C., Waldminghaus, T. & Skarstad, K. Replication patterns and organization of replication forks in Vibrio cholerae. Microbiology 157, 695–708 (2011).

    CAS  PubMed  Google Scholar 

  19. Lindas, A. C. & Bernander, R. The cell cycle of archaea. Nat. Rev. Microbiol. 11, 627–638 (2013).

    CAS  PubMed  Google Scholar 

  20. Si, F. et al. Invariance of initiation mass and predictability of cell size in Escherichia coli. Curr. Biol. 27, 1278–1287 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Zheng, H. et al. Interrogating the Escherichia coli cell cycle by cell dimension perturbations. Proc. Natl Acad. Sci. USA 113, 15000–15005 (2016).

    CAS  PubMed  Google Scholar 

  22. Wallden, M., Fange, D., Lundius, E. G., Baltekin, O. & Elf, J. The synchronization of replication and division cycles in individual E. coli cells. Cell 166, 729–739 (2016).

    CAS  PubMed  Google Scholar 

  23. Whitman, W. B., Coleman, D. C. & Wiebe, W. J. Prokaryotes: the unseen majority. Proc. Natl Acad. Sci. USA 95, 6578–6583 (1998).

    CAS  PubMed  Google Scholar 

  24. Lomstein, B. A., Langerhuus, A. T., D’Hondt, S., Jorgensen, B. B. & Spivack, A. J. Endospore abundance, microbial growth and necromass turnover in deep sub-seafloor sediment. Nature 484, 101–104 (2012).

    CAS  PubMed  Google Scholar 

  25. Rocha, E. P. & Danchin, A. Essentiality, not expressiveness, drives gene-strand bias in bacteria. Nat. Genet. 34, 377–378 (2003).

    CAS  PubMed  Google Scholar 

  26. Rocha, E. P. & Danchin, A. Gene essentiality determines chromosome organisation in bacteria. Nucleic Acids Res. 31, 6570–6577 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. De Septenville, A. L., Duigou, S., Boubakri, H. & Michel, B. Replication fork reversal after replication-transcription collision. PLOS Genet. 8, e1002622 (2012).

    PubMed  PubMed Central  Google Scholar 

  28. Wang, J. D., Berkmen, M. B. & Grossman, A. D. Genome-wide coorientation of replication and transcription reduces adverse effects on replication in Bacillus subtilis. Proc. Natl Acad. Sci. USA 104, 5608–5613 (2007).

    CAS  PubMed  Google Scholar 

  29. Bremer, H. & Dennis, P. P. Modulation of chemical composition and other parameters of the cell at different exponential growth rates. EcoSal Plus https://doi.org/10.1128/ecosal.5.2.3 (2008).

    Article  PubMed  Google Scholar 

  30. Couturier, E. & Rocha, E. P. Replication-associated gene dosage effects shape the genomes of fast-growing bacteria but only for transcription and translation genes. Mol. Microbiol. 59, 1506–1518 (2006).

    CAS  PubMed  Google Scholar 

  31. Touzain, F., Petit, M. A., Schbath, S. & El Karoui, M. DNA motifs that sculpt the bacterial chromosome. Nat. Rev. Microbiol. 9, 15–26 (2011).

    CAS  PubMed  Google Scholar 

  32. Woldringh, C. L. & Nanninga, N. Structural and physical aspects of bacterial chromosome segregation. J. Struct. Biol. 156, 273–283 (2006).

    CAS  PubMed  Google Scholar 

  33. Paulson, J. R. & Laemmli, U. K. The structure of histone-depleted metaphase chromosomes. Cell 12, 817–828 (1977).

    CAS  PubMed  Google Scholar 

  34. Kavenoff, R. & Bowen, B. C. Electron microscopy of membrane-free folded chromosomes from Escherichia coli. Chromosoma 59, 89–101 (1976).

    CAS  PubMed  Google Scholar 

  35. Wang, X., Possoz, C. & Sherratt, D. J. Dancing around the divisome: asymmetric chromosme segregation in Escherichia coli. Genes Dev. 19, 2367–2377 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Nielsen, H. J., Li, Y., Youngren, B., Hansen, F. G. & Austin, S. Progressive segregation of the Escherichia coli chromosome. Mol. Microbiol. 61, 383–393 (2006).

    CAS  PubMed  Google Scholar 

  37. Viollier, P. H. et al. Rapid and sequential movement of individual chromosomal loci to specific subcellular locations during bacterial DNA replication. Proc. Natl Acad. Sci. USA 101, 9257–9262 (2004).

    CAS  PubMed  Google Scholar 

  38. Vallet-Gely, I. & Boccard, F. Chromosomal organization and segregation in Pseudomonas aeruginosa. PLOS Genet. 9, e1003492 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. David, A. et al. The two cis-acting sites, parS1 and oriC1, contribute to the longitudinal organisation of Vibrio cholerae chromosome I. PLOS Genet. 10, e1004448 (2014).

    PubMed  PubMed Central  Google Scholar 

  40. Nasmyth, K. & Haering, C. H. The structure and function of SMC and kleisin complexes. Annu. Rev. Biochem. 74, 595–648 (2005).

    CAS  PubMed  Google Scholar 

  41. Ganji, M. et al. Real-time imaging of DNA loop extrusion by condensin. Science 360, 102–105 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Mercier, R. et al. The MatP/matS site-specific system organizes the terminus region of the E. coli chromosome into a macrodomain. Cell 135, 475–485 (2008).

    CAS  PubMed  Google Scholar 

  43. Lioy, V. S. et al. Multiscale structuring of the E. coli chromosome by nucleoid-associated and condensin proteins. Cell 172, 771–783 (2018).

    CAS  PubMed  Google Scholar 

  44. Nolivos, S. et al. MatP regulates the coordinated action of topoisomerase IV and MukBEF in chromosome segregation. Nat. Commun. 7, 10466 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Niki, H., Jaffe, A., Imamura, R., Ogura, T. & Hiraga, S. The new gene mukB codes for a 177 kd protein with coiled-coil domains involved in chromosome partitioning of E. coli. EMBO J. 10, 183–193 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Duderstadt, K. E. & Berger, J. M. AAA+ ATPases in the initiation of DNA replication. Crit. Rev. Biochem. Mol. Biol. 43, 163–187 (2008).

    CAS  PubMed  Google Scholar 

  47. Wolanski, M., Donczew, R., Zawilak-Pawlik, A. & Zakrzewska-Czerwinska, J. oriC-encoded instructions for the initiation of bacterial chromosome replication. Front. Microbiol. 5, 735 (2014).

    PubMed  Google Scholar 

  48. Grimwade, J. E. et al. Origin recognition is the predominant role for DnaA-ATP in initiation of chromosome replication. Nucleic Acids Res. 46, 6140–6151 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. McGarry, K. C., Ryan, V. T., Grimwade, J. E. & Leonard, A. C. Two discriminatory binding sites in the Escherichia coli replication origin are required for DNA strand opening by initiator DnaA-ATP. Proc. Natl Acad. Sci. USA 101, 2811–2816 (2004).

    CAS  PubMed  Google Scholar 

  50. Kawakami, H., Keyamura, K. & Katayama, T. Formation of an ATP-DnaA-specific initiation complex requires DnaA Arginine 285, a conserved motif in the AAA+ protein family. J. Biol. Chem. 280, 27420–27430 (2005).

    CAS  PubMed  Google Scholar 

  51. Rozgaja, T. A. et al. Two oppositely oriented arrays of low-affinity recognition sites in oriC guide progressive binding of DnaA during Escherichia coli pre-RC assembly. Mol. Microbiol. 82, 475–488 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Stepankiw, N., Kaidow, A., Boye, E. & Bates, D. The right half of the Escherichia coli replication origin is not essential for viability, but facilitates multi-forked replication. Mol. Microbiol. 74, 467–479 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Sakiyama, Y., Kasho, K., Noguchi, Y., Kawakami, H. & Katayama, T. Regulatory dynamics in the ternary DnaA complex for initiation of chromosomal replication in Escherichia coli. Nucleic Acids Res. 45, 12354–12373 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Kowalski, D. & Eddy, M. J. The DNA unwinding element: a novel, cis-acting component that facilitates opening of the Escherichia coli replication origin. EMBO J. 8, 4335–4344 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Kaur, G. et al. Building the bacterial orisome: high-affinity DnaA recognition plays a role in setting the conformation of oriC DNA. Mol. Microbiol. 91, 1148–1163 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Kurokawa, K., Nishida, S., Emoto, A., Sekimizu, K. & Katayama, T. Replication cycle-coordinated change of the adenine nucleotide-bound forms of DnaA protein in Escherichia coli. EMBO J. 18, 6642–6652 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Kato, J. & Katayama, T. Hda, a novel DnaA-related protein, regulates the replication cycle in Escherichia coli. EMBO J. 20, 4253–4262 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Kasho, K., Tanaka, H., Sakai, R. & Katayama, T. Cooperative DnaA binding to the negatively supercoiled datA locus stimulates DnaA-ATP hydrolysis. J. Biol. Chem. 292, 1251–1266 (2017).

    CAS  PubMed  Google Scholar 

  59. Fujimitsu, K., Senriuchi, T. & Katayama, T. Specific genomic sequences of E. coli promote replicational initiation by directly reactivating ADP-DnaA. Genes Dev. 23, 1221–1233 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Sekimizu, K. & Kornberg, A. Cardiolipin activation of dnaA protein, the initiation protein of replication in Escherichia coli. J. Biol. Chem. 263, 7131–7135 (1988).

    CAS  PubMed  Google Scholar 

  61. Flatten, I., Fossum-Raunehaug, S., Taipale, R., Martinsen, S. & Skarstad, K. The DnaA protein is not the limiting factor for initiation of replication in Escherichia coli. PLOS Genet. 11, e1005276 (2015).

    PubMed  PubMed Central  Google Scholar 

  62. Campbell, J. L. & Kleckner, N. E. coli oriC and the dnaA gene promoter are sequestered from dam methyltransferase following the passage of the chromosomal replication fork. Cell 62, 967–979 (1990).

    CAS  PubMed  Google Scholar 

  63. Nievera, C., Torgue, J. J., Grimwade, J. E. & Leonard, A. C. SeqA blocking of DnaA-oriC interactions ensures staged assembly of the E. coli pre-RC. Mol. Cell 24, 581–592 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Leonard, A. C. & Grimwade, J. E. The orisome: structure and function. Front. Microbiol. 6, 545 (2015).

    PubMed  PubMed Central  Google Scholar 

  65. Hansen, F. G. & Atlung, T. The DnaA tale. Front. Microbiol. 9, 319 (2018).

    PubMed  PubMed Central  Google Scholar 

  66. Katayama, T., Kasho, K. & Kawakami, H. The DnaA cycle in Escherichia coli: activation, function and inactivation of the initiator protein. Front. Microbiol. 8, 2496 (2017).

    PubMed  PubMed Central  Google Scholar 

  67. Skarstad, K. & Katayama, T. Regulating DNA replication in bacteria. Cold Spring Harb. Perspect. Biol. 5, a012922 (2013).

    PubMed  PubMed Central  Google Scholar 

  68. Kurokawa, K. et al. Rapid exchange of bound ADP on the Staphylococcus aureus replication initiation protein DnaA. J. Biol. Chem. 284, 34201–34210 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Scholefield, G. & Murray, H. YabA and DnaD inhibit helix assembly of the DNA replication initiation protein DnaA. Mol. Microbiol. 90, 147–159 (2013).

    CAS  PubMed  Google Scholar 

  70. Scholefield, G., Errington, J. & Murray, H. Soj/ParA stalls DNA replication by inhibiting helix formation of the initiator protein DnaA. EMBO J. 31, 1542–1555 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Collier, J. & Shapiro, L. Feedback control of DnaA-mediated replication initiation by replisome-associated HdaA protein in Caulobacter. J. Bacteriol. 191, 5706–5716 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Wargachuk, R. & Marczynski, G. T. The Caulobacter crescentus homolog of DnaA (HdaA) also regulates the proteolysis of the replication initiator protein DnaA. J. Bacteriol. 197, 3521–3532 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Jonas, K., Chen, Y. E. & Laub, M. T. Modularity of the bacterial cell cycle enables independent spatial and temporal control of DNA replication. Curr. Biol. 21, 1092–1101 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Bastedo, D. P. & Marczynski, G. T. CtrA response regulator binding to the Caulobacter chromosome replication origin is required during nutrient and antibiotic stress as well as during cell cycle progression. Mol. Microbiol. 72, 139–154 (2009).

    CAS  PubMed  Google Scholar 

  75. Val, M. E., Soler-Bistue, A., Bland, M. J. & Mazel, D. Management of multipartite genomes: the Vibrio cholerae model. Curr. Opin. Microbiol. 22, 120–126 (2014).

    CAS  PubMed  Google Scholar 

  76. Nordstrom, K. & Dasgupta, S. Copy-number control of the Escherichia coli chromosome: a plasmidologist’s view. EMBO Rep. 7, 484–489 (2006).

    PubMed  PubMed Central  Google Scholar 

  77. Tolmasky, M. & Alonso, J. C. Plasmids: Biology and Impact in Biotechnology and Discovery (ASM Press, 2015).

  78. Rasmussen, T., Jensen, R. B. & Skovgaard, O. The two chromosomes of Vibrio cholerae are initiated at different time points in the cell cycle. EMBO J. 26, 3124–3131 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Frage, B. et al. Spatiotemporal choreography of chromosome and megaplasmids in the Sinorhizobium meliloti cell cycle. Mol. Microbiol. 100, 808–823 (2016).

    CAS  PubMed  Google Scholar 

  80. Deghelt, M. et al. G1-arrested newborn cells are the predominant infectious form of the pathogen Brucella abortus. Nat. Commun. 5, 4366 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Du, W. L. et al. Orderly replication and segregation of the four replicons of Burkholderia cenocepacia J2315. PLOS Genet. 12, e1006172 (2016).

    PubMed  PubMed Central  Google Scholar 

  82. Baek, J. H. & Chattoraj, D. K. Chromosome I controls chromosome II replication in Vibrio cholerae. PLOS Genet. 10, e1004184 (2014).

    PubMed  PubMed Central  Google Scholar 

  83. Pal, D., Venkova-Canova, T., Srivastava, P. & Chattoraj, D. K. Multipartite regulation of rctB, the replication initiator gene of Vibrio cholerae chromosome II. J. Bacteriol. 187, 7167–7175 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Duigou, S. et al. Independent control of replication initiation of the two Vibrio cholerae chromosomes by DnaA and RctB. J. Bacteriol. 188, 6419–6424 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Val, M. E. et al. A checkpoint control orchestrates the replication of the two chromosomes of Vibrio cholerae. Sci. Adv. 2, e1501914 (2016).

    PubMed  PubMed Central  Google Scholar 

  86. Griese, M., Lange, C. & Soppa, J. Ploidy in cyanobacteria. FEMS Microbiol. Lett. 323, 124–131 (2011).

    CAS  PubMed  Google Scholar 

  87. Ohbayashi, R. et al. DNA replication depends on photosynthetic electron transport in cyanobacteria. FEMS Microbiol. Lett. 344, 138–144 (2013).

    CAS  PubMed  Google Scholar 

  88. Watanabe, S. et al. Light-dependent and asynchronous replication of cyanobacterial multi-copy chromosomes. Mol. Microbiol. 83, 856–865 (2012).

    CAS  PubMed  Google Scholar 

  89. Chen, A. H., Afonso, B., Silver, P. A. & Savage, D. F. Spatial and temporal organization of chromosome duplication and segregation in the cyanobacterium Synechococcus elongatus PCC 7942. PLOS ONE 7, e47837 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Jain, I. H., Vijayan, V. & O’Shea, E. K. Spatial ordering of chromosomes enhances the fidelity of chromosome partitioning in cyanobacteria. Proc. Natl Acad. Sci. USA 109, 13638–13643 (2012).

    CAS  PubMed  Google Scholar 

  91. Paijmans, J., Bosman, M., Ten Wolde, P. R. & Lubensky, D. K. Discrete gene replication events drive coupling between the cell cycle and circadian clocks. Proc. Natl Acad. Sci. USA 113, 4063–4068 (2016).

    CAS  PubMed  Google Scholar 

  92. Mendell, J. E., Clements, K. D., Choat, J. H. & Angert, E. R. Extreme polyploidy in a large bacterium. Proc. Natl Acad. Sci. USA 105, 6730–6734 (2008).

    CAS  PubMed  Google Scholar 

  93. Kornberg, A. & Baker, T. DNA Replication 2nd edn (Freeman, 1992).

  94. Trojanowski, D. et al. Choreography of the Mycobacterium replication machinery during the cell cycle. mBio 6, e02125-14 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Churchward, G. & Bremer, H. Determination of deoxyribonucleic acid replication time in exponentially growing Escherichia coli B/r. J. Bacteriol. 130, 1206–1213 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Allman, R., Schjerven, T. & Boye, E. Cell cycle parameters of Escherichia coli K-12. J. Bacteriol. 173, 7970–7974 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Lewis, J. S., Jergic, S. & Dixon, N. E. The E. coli DNA replication fork. Enzymes 39, 31–88 (2016).

    CAS  PubMed  Google Scholar 

  98. Beattie, T. R. & Reyes-Lamothe, R. A replisome’s journey through the bacterial chromosome. Front. Microbiol. 6, 562 (2015).

    PubMed  PubMed Central  Google Scholar 

  99. Beattie, T. R. et al. Frequent exchange of the DNA polymerase during bacterial chromosome replication. eLife 6, e21763 (2017).

    PubMed  PubMed Central  Google Scholar 

  100. Lewis, J. S. et al. Single-molecule visualization of fast polymerase turnover in the bacterial replisome. Elife 6, e23932 (2017).

    PubMed  PubMed Central  Google Scholar 

  101. Liao, Y., Li, Y., Schroeder, J. W., Simmons, L. A. & Biteen, J. S. Single-molecule DNA polymerase dynamics at a bacterial replisome in live cells. Biophys. J. 111, 2562–2569 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Robinson, A., Causer, R. J. & Dixon, N. E. Architecture and conservation of the bacterial DNA replication machinery, an underexploited drug target. Curr. Drug Targets 13, 352–372 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Zaritsky, A. & Pritchard, R. H. Changes in cell size and shape associated with changes in the replication time of the chromosome of Escherichia coli. J. Bacteriol. 114, 824–837 (1973).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Morigen, Odsbu,I. & Skarstad, K. A reduction in ribonucleotide reductase activity slows down the chromosome replication fork but does not change its localization. PLOS ONE 4, e7617 (2009).

    PubMed  PubMed Central  Google Scholar 

  105. Zhu, M. et al. Manipulating the bacterial cell cycle and cell size by titrating the expression of ribonucleotide reductase. mBio 8, e01741-17 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Olliver, A., Saggioro, C., Herrick, J. & Sclavi, B. DnaA-ATP acts as a molecular switch to control levels of ribonucleotide reductase expression in Escherichia coli. Mol. Microbiol. 76, 1555–1571 (2010).

    CAS  PubMed  Google Scholar 

  107. Hanke, P. D. & Fuchs, J. A. Regulation of ribonucleoside diphosphate reductase mRNA synthesis in. Escherichia coli. J. Bacteriol. 154, 1040–1045 (1983).

    CAS  PubMed  Google Scholar 

  108. Torrents, E. et al. NrdR controls differential expression of the Escherichia coli ribonucleotide reductase genes. J. Bacteriol. 189, 5012–5021 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Gon, S. et al. A novel regulatory mechanism couples deoxyribonucleotide synthesis and DNA replication in Escherichia coli. EMBO J. 25, 1137–1147 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Babu, V. M. P., Itsko, M., Baxter, J. C., Schaaper, R. M. & Sutton, M. D. Insufficient levels of the nrdAB-encoded ribonucleotide reductase underlie the severe growth defect of the Deltahda E. coli strain. Mol. Microbiol. 104, 377–399 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. McKethan, B. L. & Spiro, S. Cooperative and allosterically controlled nucleotide binding regulates the DNA binding activity of NrdR. Mol. Microbiol. 90, 278–289 (2013).

    CAS  PubMed  Google Scholar 

  112. Denapoli, J., Tehranchi, A. K. & Wang, J. D. Dose-dependent reduction of replication elongation rate by (p)ppGpp in Escherichia coli and Bacillus subtilis. Mol. Microbiol. 88, 93–104 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Wang, J. D., Sanders, G. M. & Grossman, A. D. Nutritional control of elongation of DNA replication by (p)ppGpp. Cell 128, 865–875 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Christensen, R. B., Christensen, J. R., Koenig, I. & Lawrence, C. W. Untargeted mutagenesis induced by UV in the lacI gene of Escherichia coli. Mol. Gen. Genet. 201, 30–34 (1985).

    CAS  PubMed  Google Scholar 

  115. Wendel, B. M., Cole, J. M., Courcelle, C. T. & Courcelle, J. SbcC-SbcD and ExoI process convergent forks to complete chromosome replication. Proc. Natl Acad. Sci. USA 115, 349–354 (2018).

    CAS  PubMed  Google Scholar 

  116. Midgley-Smith, S. L. et al. Chromosomal over-replication in Escherichia coli recG cells is triggered by replication fork fusion and amplified if replichore symmetry is disturbed. Nucleic Acids Res. 46, 7701–7715 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Sinha, A. K. et al. Division-induced DNA double strand breaks in the chromosome terminus region of Escherichia coli lacking RecBCD DNA repair enzyme. PLOS Genet. 13, e1006895 (2017).

    PubMed  PubMed Central  Google Scholar 

  118. Wang, X., Montero Llopis, P. & Rudner, D. Z. Organization and segregation of bacterial chromosomes. Nat. Rev. Genet. 14, 191–203 (2013).

    CAS  PubMed  Google Scholar 

  119. Adams, D. W., Wu, L. J. & Errington, J. Cell cycle regulation by the bacterial nucleoid. Curr. Opin. Microbiol. 22, 94–101 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Postow, L., Crisona, N. J., Peter, B. J., Hardy, C. D. & Cozzarelli, N. R. Topological challenges to DNA replication: conformations at the fork. Proc. Natl Acad. Sci. USA 98, 8219–8226 (2001).

    CAS  PubMed  Google Scholar 

  121. Wang, X., Reyes-Lamothe, R. & Sherratt, D. J. Modulation of Escherichia coli sister chromosome cohesion by topoisomerase IV. Genes Dev. 22, 2426–2433 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Joshi, M. C. et al. Regulation of sister chromosome cohesion by the replication fork tracking protein SeqA. PLOS Genet. 9, e1003673 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Barre, F. X. & Sherratt, D. in The Bacterial Chromosome Ch. 28 (ed. Higgins, N. P.) 513–524 (ASM Press, 2005).

  124. Ip, S. C., Bregu, M., Barre, F. X. & Sherratt, D. J. Decatenation of DNA circles by FtsK-dependent Xer site-specific recombination. EMBO J. 22, 6399–6407 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Grainge, I. et al. Unlinking chromosome catenanes in vivo by site-specific recombination. EMBO J. 26, 4228–4238 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Jun, S. & Wright, A. Entropy as the driver of chromosome segregation. Nat. Rev. Microbiol. 8, 600–607 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Kennedy, S. P., Chevalier, F. & Barre, F. X. Delayed activation of Xer recombination at dif by FtsK during septum assembly in Escherichia coli. Mol. Microbiol. 68, 1018–1028 (2008).

    CAS  PubMed  Google Scholar 

  128. Hobbie, J. E. & Hobbie, E. A. Microbes in nature are limited by carbon and energy: the starving-survival lifestyle in soil and consequences for estimating microbial rates. Front. Microbiol. 4, 324 (2013).

    PubMed  PubMed Central  Google Scholar 

  129. Slager, J., Kjos, M., Attaiech, L. & Veening, J. W. Antibiotic-induced replication stress triggers bacterial competence by increasing gene dosage near the origin. Cell 157, 395–406 (2014).

    CAS  PubMed  Google Scholar 

  130. Ohbayashi, R. et al. Diversification of DnaA dependency for DNA replication in cyanobacterial evolution. ISME J. 10, 1113–1121 (2016).

    CAS  PubMed  Google Scholar 

  131. Errington, J. L-Form bacteria, cell walls and the origins of life. Open Biol. 3, 120143 (2013).

    PubMed  PubMed Central  Google Scholar 

  132. Potvin-Trottier, L., Luro, S. & Paulsson, J. Microfluidics and single-cell microscopy to study stochastic processes in bacteria. Curr. Opin. Microbiol. 43, 186–192 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Ullman, G. et al. High-throughput gene expression analysis at the level of single proteins using a microfluidic turbidostat and automated cell tracking. Phil. Trans. R. Soc. B 368, 20120025 (2013).

    CAS  PubMed  Google Scholar 

  134. Uphoff, S. et al. Stochastic activation of a DNA damage response causes cell-to-cell mutation rate variation. Science 351, 1094–1097 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Liu, J. et al. Coupling between distant biofilms and emergence of nutrient time-sharing. Science 356, 638–642 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Din, M. O. et al. Synchronized cycles of bacterial lysis for in vivo delivery. Nature 536, 81–85 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Massalha, H., Korenblum, E., Malitsky, S., Shapiro, O. H. & Aharoni, A. Live imaging of root-bacteria interactions in a microfluidics setup. Proc. Natl Acad. Sci. USA 114, 4549–4554 (2017).

    CAS  PubMed  Google Scholar 

  138. Walsh, E. J. et al. Microfluidics with fluid walls. Nat. Commun. 8, 816 (2017).

    PubMed  PubMed Central  Google Scholar 

  139. Lawson, M. J. et al. In situ genotyping of a pooled strain library after characterizing complex phenotypes. Mol. Syst. Biol. 13, 947 (2017).

    PubMed  PubMed Central  Google Scholar 

  140. Campos, M. et al. Genomewide phenotypic analysis of growth, cell morphogenesis, and cell cycle events in Escherichia coli. Mol. Syst. Biol. 14, e7573 (2018).

    PubMed  PubMed Central  Google Scholar 

  141. Helmstetter, C. E. DNA synthesis during the division cycle of rapidly growing Escherichia coli B/r. J. Mol. Biol. 31, 507–518 (1968).

    CAS  PubMed  Google Scholar 

  142. Skarstad, K., Boye, E. & Steen, H. B. Timing of initiation of chromosome replication in individual Escherichia coli cells. EMBO J. 5, 1711–1717 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Michelsen, O., Teixeira de Mattos, M. J., Jensen, P. R. & Hansen, F. G. Precise determinations of C and D periods by flow cytometry in Escherichia coli K-12 and B/r. Microbiology 149, 1001–1010 (2003).

    CAS  PubMed  Google Scholar 

  144. Reyes-Lamothe, R., Possoz, C., Danilova, O. & Sherratt, D. J. Independent positioning and action of Escherichia coli replisomes in live cells. Cell 133, 90–102 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Jensen, R. B., Wang, S. C. & Shapiro, L. A moving DNA replication factory in Caulobacter crescentus. EMBO J. 20, 4952–4963 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Cook, P. R. The organization of replication and transcription. Science 284, 1790–1795 (1999).

    CAS  PubMed  Google Scholar 

  147. Lemon, K. P. & Grossman, A. D. Localization of bacterial DNA polymerase: evidence for a factory model of replication. Science 282, 1516–1519 (1998).

    CAS  PubMed  Google Scholar 

  148. Mangiameli, S. M., Veit, B. T., Merrikh, H. & Wiggins, P. A. The replisomes remain spatially proximal throughout the cell cycle in bacteria. PLOS Genet. 13, e1006582 (2017).

    PubMed  PubMed Central  Google Scholar 

  149. Reyes-Lamothe, R., Sherratt, D. J. & Leake, M. C. Stoichiometry and architecture of active DNA replication machinery in Escherichia coli. Science 328, 498–501 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Arias-Cartin, R. et al. Replication fork passage drives asymmetric dynamics of a critical nucleoid-associated protein in Caulobacter. EMBO J. 36, 301–318 (2017).

    CAS  PubMed  Google Scholar 

  151. Breier, A. M., Weier, H.-U. G. & Cozzarelli, N. R. Independence of replisomes in Escherichia coli chromosomal replication. Proc. Natl Acad. Sci. USA 102, 3942–3947 (2005).

    CAS  PubMed  Google Scholar 

  152. Bates, D. & Kleckner, N. Chromosome and replisome dynamics in E. coli: loss of sister cohesion triggers global chromosome movement and mediates chromosome segregation. Cell 121, 899–911 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Skarstad, K., Steen, H. B. & Boye, E. Cell cycle parameters of slowly growing Escherichia coli B/r studied by flow cytometry. J. Bacteriol. 154, 656–662 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Skarstad, K., Steen, H. B. & Boye, E. Escherichia coli DNA distributions measured by flow cytometry and compared with theoretical computer simulations. J. Bacteriol. 163, 661–668 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Marczynski, G. T., Dingwall, A. & Shapiro, L. Plasmid and chromosomal DNA replication and partitioning during the Caulobacter crescentus cell cycle. J. Mol. Biol. 212, 709–722 (1990).

    CAS  PubMed  Google Scholar 

  156. Le, T. B., Imakaev, M. V., Mirny, L. A. & Laub, M. T. High-resolution mapping of the spatial organization of a bacterial chromosome. Science 342, 731–734 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Research in the Reyes-Lamothe laboratory is funded by the Natural Sciences and Engineering Research Council of Canada (NSERC# 435521–2013), the Canadian Institutes for Health Research (CIHR MOP# 142473) and the Canada Research Chairs programme. The Sherratt laboratory is funded by a Wellcome Investigator Award (200782/Z/16/Z). The authors thank many colleagues for stimulating discussions, in particular S. Uphoff and B. Novak (University of Oxford) and members of the Reyes-Lamothe laboratory.

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Nature Reviews Microbiology thanks T. Katayama and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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R.R.-L. and D.J.S. researched data for the article, substantially contributed to the discussion of content, wrote the article and reviewed and edited the article before submission.

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Correspondence to Rodrigo Reyes-Lamothe or David J. Sherratt.

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Glossary

Replichores

Two chromosomal halves starting at the replication origin, each replicated by a different replication fork.

Generation time

Average time from birth to division.

Replication forks

Y-shaped DNA structures formed at the point where DNA is unwound during DNA replication.

Nucleoid occlusion

The process by which the presence of nucleoid DNA prevents the formation of an FtsZ ring and divisome over that DNA.

Stalked cells

Sessile, proliferative Caulobacter crescentus cells.

Swarmer cells

Motile Caulobacter crescentus cells that do not replicate.

Iteron plasmids

Characterized by a replication origin composed of repeated sequences that bind to a cognate initiator protein.

Primase

Replisome subunit that synthesizes short RNA primers which are then elongated by the DNA polymerase.

SOS response

Cellular response to DNA damage leading to inhibition of cell division and induction of DNA repair systems.

Divisome

Structure that forms around the middle of the cell, composed of multiple proteins required for cell division.

Cohesion time

Time from the replication of a locus to the separation of the newly replicated sister loci.

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Reyes-Lamothe, R., Sherratt, D.J. The bacterial cell cycle, chromosome inheritance and cell growth. Nat Rev Microbiol 17, 467–478 (2019). https://doi.org/10.1038/s41579-019-0212-7

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