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The ABCs of plasmid replication and segregation

Abstract

To ensure faithful transmission of low-copy plasmids to daughter cells, these plasmids must replicate once per cell cycle and distribute the replicated DNA to the nascent daughter cells. RepABC family plasmids are found exclusively in alphaproteobacteria and carry a combined replication and partitioning locus, the repABC cassette, which is also found on secondary chromosomes in this group. RepC and a replication origin are essential for plasmid replication, and RepA, RepB and the partitioning sites distribute the replicons to predivisional cells. Here, we review our current understanding of the transcriptional and post-transcriptional regulation of the Rep proteins and of their functions in plasmid replication and partitioning.

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Figure 1: Replication and partitioning of low-copy plasmids.
Figure 2: Genetic organization of repABC systems from representative RepABC plasmids.
Figure 3: Regulation of the repABC operon of octopine-type tumour-inducing (Ti) plasmids.
Figure 4: RNA RepE on the control of repC expression.

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References

  1. Slater, S. et al. in Agrobacterium: From Biology to Biotechnology 149–181 (eds Tzfira, T. & Citovsky, V.) (Springer, 2008).

    Book  Google Scholar 

  2. Bailly, X. et al. Population genomics of Sinorhizobium medicae based on low-coverage sequencing of sympatric isolates. ISME J. 5, 1722–1734 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Harrison, P. W., Lower, R. P., Kim, N. K. & Young, J. P. Introducing the bacterial 'chromid': not a chromosome, not a plasmid. Trends Microbiol. 18, 141–148 (2010). In this work, it is argued that secondary chromosomes should be conceived as a distinct class of molecules.

    Article  CAS  PubMed  Google Scholar 

  4. Thomas, C. M. Paradigms of plasmid organization. Mol. Microbiol. 37, 485–491 (2000). This review concisely explores the structural traits, as well as the survival and propagation strategies, of plasmids.

    Article  CAS  PubMed  Google Scholar 

  5. Austin, S., Ziese, M. & Sternberg, N. A novel role for site-specific recombination in maintenance of bacterial replicons. Cell 25, 729–736 (1981).

    Article  CAS  PubMed  Google Scholar 

  6. Summers, D. Timing, self-control and a sense of direction are the secrets of multicopy plasmid stability. Mol. Microbiol. 29, 1137–1145 (1998).

    Article  CAS  PubMed  Google Scholar 

  7. Sengupta, M. & Austin, S. The prevalence and significance of plasmid maintenance functions in the virulence plasmids of pathogenic bacteria. Infect. Immun. 79, 2502–2509 (2011). This recent review describes plasmid maintenance functions, such as active partitioning, multimer resolution and post-segregational killing, as bona fide virulence factors.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Engelberg-Kulka, H. & Glaser, G. Addiction modules and programmed cell death and antideath in bacterial cultures. Annu. Rev. Microbiol. 53, 43–70 (1999).

    Article  CAS  PubMed  Google Scholar 

  9. Sia, E. A., Roberts, R. C., Easter, C., Helinski, D. R. & Figurski, D. H. Different relative importances of the par operons and the effect of conjugal transfer on the maintenance of intact promiscuous plasmid RK2. J. Bacteriol. 177, 2789–2797 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tabata, S., Hooykaas, P. J. & Oka, A. Sequence determination and characterization of the replicator region in the tumor-inducing plasmid pTiB6S3. J. Bacteriol. 171, 1665–1672 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Castillo-Ramirez, S., Vazquez-Castellanos, J. F., Gonzalez, V. & Cevallos, M. A. Horizontal gene transfer and diverse functional constraints within a common replication-partitioning system in Alphaproteobacteria: the repABC operon. BMC Genomics 10, 536 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cevallos, M. A., Cervantes-Rivera, R. & Gutierrez-Rios, R. M. The repABC plasmid family. Plasmid 60, 19–37 (2008).

    Article  CAS  PubMed  Google Scholar 

  13. Petersen, J., Brinkmann, H. & Pradella, S. Diversity and evolution of repABC type plasmids in Rhodobacterales. Environ. Microbiol. 11, 2627–2638 (2009).

    Article  CAS  PubMed  Google Scholar 

  14. Slater, S. C. et al. Genome sequences of three Agrobacterium biovars help elucidate the evolution of multichromosome genomes in bacteria. J. Bacteriol. 191, 2501–2511 (2009). This study offers insightful hypotheses on replicon evolution in alphaproteobacteria.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pappas, K. M. & Cevallos, M. A. in Biocommunication of Soil Microorganisms (ed. Witzany, G.) 295–338 (Springer, 2010). This book chapter describes repABC plasmids in the family Rhizobiaceae and their role in cell–cell communication.

    Google Scholar 

  16. Petersen, J. et al. Origin and evolution of a novel DnaA-like plasmid replication type in Rhodobacterales. Mol. Biol. Evol. 28, 1229–1240 (2011).

    Article  CAS  PubMed  Google Scholar 

  17. Petersen, J. et al. Think pink: photosynthesis, plasmids and the Roseobacter clade. Environ. Microbiol. 26 Jun 2012 (doi:10.1111/j.1462-2920.2012.02806.x).

    Article  CAS  PubMed  Google Scholar 

  18. Chai, Y. & Winans, S. C. A small antisense RNA downregulates expression of an essential replicase protein of an Agrobacterium tumefaciens Ti plasmid. Mol. Microbiol. 56, 1574–1585 (2005).

    Article  CAS  PubMed  Google Scholar 

  19. Cevallos, M. A. et al. Rhizobium etli CFN42 contains at least three plasmids of the repABC family: a structural and evolutionary analysis. Plasmid 48, 104–116 (2002).

    Article  CAS  PubMed  Google Scholar 

  20. MacLellan, S. R., Smallbone, L. A., Sibley, C. D. & Finan, T. M. The expression of a novel antisense gene mediates incompatibility within the large repABC family of α-proteobacterial plasmids. Mol. Microbiol. 55, 611–623 (2005).

    Article  CAS  PubMed  Google Scholar 

  21. Pappas, K. M. Cell–cell signaling and the Agrobacterium tumefaciens Ti plasmid copy number fluctuations. Plasmid 60, 89–107 (2008).

    Article  CAS  PubMed  Google Scholar 

  22. Venkova-Canova, T., Soberon, N. E., Ramirez-Romero, M. A. & Cevallos, M. A. Two discrete elements are required for the replication of a repABC plasmid: an antisense RNA and a stem–loop structure. Mol. Microbiol. 54, 1431–1444 (2004). A comprehensive study that, together with references 18 and 20, demonstrates the role of antisense regulation in repC expression.

    Article  CAS  PubMed  Google Scholar 

  23. Bartosik, D., Wlodarczyk, M. & Thomas, C. M. Complete nucleotide sequence of the replicator region of Paracoccus (Thiobacillus) versutus pTAV1 plasmid and its correlation to several plasmids of Agrobacterium and Rhizobium species. Plasmid 38, 53–59 (1997).

    Article  CAS  PubMed  Google Scholar 

  24. Bartosik, D., Baj, J. & Wlodarczyk, M. Molecular and functional analysis of pTAV320, a repABC-type replicon of the Paracoccus versutus composite plasmid pTAV1. Microbiology 144, 3149–3157 (1998).

    Article  CAS  PubMed  Google Scholar 

  25. Gonzalez, V. et al. The partitioned Rhizobium etli genome: genetic and metabolic redundancy in seven interacting replicons. Proc. Natl Acad. Sci. USA 103, 3834–3839 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Galibert, F. et al. The composite genome of the legume symbiont Sinorhizobium meliloti. Science 293, 668–672 (2001).

    Article  CAS  PubMed  Google Scholar 

  27. Goodner, B. et al. Genome sequence of the plant pathogen and biotechnology agent Agrobacterium tumefaciens C58. Science 294, 2323–2328 (2001).

    Article  CAS  PubMed  Google Scholar 

  28. Wood, D. W. et al. The genome of the natural genetic engineer Agrobacterium tumefaciens C58. Science 294, 2317–2323 (2001).

    Article  CAS  PubMed  Google Scholar 

  29. Dolowy, P., Mondzelewski, J., Zawadzka, R., Baj, J. & Bartosik, D. Cloning and characterization of a region responsible for the maintenance of megaplasmid pTAV3 of Paracoccus versutus UW1. Plasmid 53, 239–250 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. Bartosik, D., Szymanik, M. & Wysocka, E. Identification of the partitioning site within the repABC-type replicon of the composite Paracoccus versutus plasmid pTAV1. J. Bacteriol. 183, 6234–6243 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bartosik, D., Baj, J., Bartosik, A. A. & Wlodarczyk, M. Characterization of the replicator region of megaplasmid pTAV3 of Paracoccus versutus and search for plasmid-encoded traits. Microbiology 148, 871–881 (2002).

    Article  CAS  PubMed  Google Scholar 

  32. Pappas, K. M. & Winans, S. C. A. LuxR-type regulator from Agrobacterium tumefaciens elevates Ti plasmid copy number by activating transcription of plasmid replication genes. Mol. Microbiol. 48, 1059–1073 (2003).

    Article  CAS  PubMed  Google Scholar 

  33. Ramirez-Romero, M. A. et al. RepA negatively autoregulates the transcription of the repABC operon of the Rhizobium etli symbiotic plasmid basic replicon. Mol. Microbiol. 42, 195–204 (2001).

    Article  CAS  PubMed  Google Scholar 

  34. Pappas, K. M. & Winans, S. C. The RepA and RepB autorepressors and TraR play opposing roles in the regulation of a Ti plasmid repABC operon. Mol. Microbiol. 49, 441–455 (2003).

    Article  CAS  PubMed  Google Scholar 

  35. Ramirez-Romero, M. A., Soberon, N., Perez-Oseguera, A., Tellez-Sosa, J. & Cevallos, M. A. Structural elements required for replication and incompatibility of the Rhizobium etli symbiotic plasmid. J. Bacteriol. 182, 3117–3124 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chai, Y. & Winans, S. C. RepB protein of an Agrobacterium tumefaciens Ti plasmid binds to two adjacent sites between repA and repB for plasmid partitioning and autorepression. Mol. Microbiol. 58, 1114–1129 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. Brilli, M. et al. The diversity and evolution of cell cycle regulation in alpha-proteobacteria: a comparative genomic analysis. BMC Syst. Biol. 4, 52 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Burgos, P. A., Velazquez, E. & Toro, N. Identification and distribution of plasmid-type A replicator region in rhizobia. Mol. Plant Microbe Interact. 9, 843–849 (1996).

    Article  CAS  PubMed  Google Scholar 

  39. Palmer, K. M., Turner, S. L. & Young, J. P. Sequence diversity of the plasmid replication gene repC in the Rhizobiaceae. Plasmid 44, 209–219 (2000).

    Article  CAS  PubMed  Google Scholar 

  40. Mercado-Blanco, J. & Olivares, J. The large nonsymbiotic plasmid pRmeGR4a of Rhizobium meliloti GR4 encodes a protein involved in replication that has homology with the RepC protein of Agrobacterium plasmids. Plasmid 32, 75–79 (1994).

    Article  CAS  PubMed  Google Scholar 

  41. Izquierdo, J. et al. An antisense RNA plays a central role in the replication control of a repC plasmid. Plasmid 54, 259–277 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Cervantes-Rivera, R., Pedraza-Lopez, F., Perez-Segura, G. & Cevallos, M. A. The replication origin of a repABC plasmid. BMC Microbiol. 11, 158 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Pinto, U. M., Flores-Mireles, A. L., Costa, E. D. & Winans, S. C. RepC protein of the octopine-type Ti plasmid binds to the probable origin of replication within repC and functions only in cis. Mol. Microbiol. 81, 1593–1606 (2011). The first biochemical study of RepC and its interaction with the putative origin of replication.

    Article  CAS  PubMed  Google Scholar 

  44. Denniston-Thompson, K., Moore, D. D., Kruger, K. E., Furth, M. E. & Blattner, F. R. Physical structure of the replication origin of bacteriophage lambda. Science 198, 1051–1056 (1977).

    Article  CAS  PubMed  Google Scholar 

  45. Scherer, G. Nucleotide sequence of the O gene and of the origin of replication in bacteriophage lambda DNA. Nucleic Acids Res. 5, 3141–3156 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Francia, M. V., Fujimoto, S., Tille, P., Weaver, K. E. & Clewell, D. B. Replication of Enterococcus faecalis pheromone-responding plasmid pAD1: location of the minimal replicon and oriV site and RepA involvement in initiation of replication. J. Bacteriol. 186, 5003–5016 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Gering, M., Gotz, F. & Bruckner, R. Sequence and analysis of the replication region of the Staphylococcus xylosus plasmid pSX267. Gene 182, 117–122 (1996).

    Article  CAS  PubMed  Google Scholar 

  48. Kwong, S. M., Skurray, R. A. & Firth, N. Staphylococcus aureus multiresistance plasmid pSK41: analysis of the replication region, initiator protein binding and antisense RNA regulation. Mol. Microbiol. 51, 497–509 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Tanaka, T., Ishida, H. & Maehara, T. Characterization of the replication region of plasmid pLS32 from the Natto strain of Bacillus subtilis. J. Bacteriol. 187, 4315–4326 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ravin, N. V., Kuprianov, V. V., Gilcrease, E. B. & Casjens, S. R. Bidirectional replication from an internal ori site of the linear N15 plasmid prophage. Nucleic Acids Res. 31, 6552–6560 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Rajewska, M., Wegrzyn, K. & Konieczny, I. AT-rich region and repeated sequences – the essential elements of replication origins of bacterial replicons. FEMS Microbiol. Rev. 36, 408–434 (2012).

    Article  CAS  PubMed  Google Scholar 

  52. Schneider, S., Zhang, W., Soultanas, P. & Paoli, M. Structure of the N-terminal oligomerization domain of DnaD reveals a unique tetramerization motif and provides insights into scaffold formation. J. Mol. Biol. 376, 1237–1250 (2008).

    Article  CAS  PubMed  Google Scholar 

  53. Wilkinson, S. P. & Grove, A. Ligand-responsive transcriptional regulation by members of the MarR family of winged helix proteins. Curr. Issues Mol. Biol. 8, 51–62 (2006).

    PubMed  Google Scholar 

  54. Masai, H. & Arai, K. RepA protein- and oriR-dependent initiation of R1 plasmid replication: identification of a rho-dependent transcription terminator required for cis-action of RepA protein. Nucleic Acids Res. 16, 6493–6514 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Dong, X. N., Womble, D. D. & Rownd, R. H. In-vivo studies on the cis-acting replication initiator protein of IncFII plasmid NR1. J. Mol. Biol. 202, 495–509 (1988).

    Article  CAS  PubMed  Google Scholar 

  56. Praszkier, J. & Pittard, A. J. Role of CIS in replication of an IncB plasmid. J. Bacteriol. 181, 2765–2772 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. del Solar, G., Giraldo, R., Ruiz-Echevarria, M. J., Espinosa, M. & Diaz-Orejas, R. Replication and control of circular bacterial plasmids. Microbiol. Mol. Biol. Rev. 62, 434–464 (1998). A comprehensive review of plasmid replication mechanisms and their controls.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Messer, W. The bacterial replication initiator DnaA. DnaA and oriC, the bacterial mode to initiate DNA replication. FEMS Microbiol. Rev. 26, 355–374 (2002).

    CAS  PubMed  Google Scholar 

  59. MacLellan, S. R., Zaheer, R., Sartor, A. L., MacLean, A. M. & Finan, T. M. Identification of a megaplasmid centromere reveals genetic structural diversity within the repABC family of basic replicons. Mol. Microbiol. 59, 1559–1575 (2006).

    Article  CAS  PubMed  Google Scholar 

  60. Gallie, D. R., Hagiya, M. & Kado, C. I. Analysis of Agrobacterium tumefaciens plasmid pTiC58 replication region with a novel high-copy-number derivative. J. Bacteriol. 161, 1034–1041 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Dunham, T. D., Xu, W., Funnell, B. E. & Schumacher, M. A. Structural basis for ADP-mediated transcriptional regulation by P1 and P7 ParA. EMBO J. 28, 1792–1802 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Soberon, N., Venkova-Canova, T., Ramirez-Romero, M. A., Tellez-Sosa, J. & Cevallos, M. A. Incompatibility and the partitioning site of the repABC basic replicon of the symbiotic plasmid from Rhizobium etli. Plasmid 51, 203–216 (2004).

    Article  CAS  PubMed  Google Scholar 

  63. Kahng, L. S. & Shapiro, L. Polar localization of replicon origins in the multipartite genomes of Agrobacterium tumefaciens and Sinorhizobium meliloti. J. Bacteriol. 185, 3384–3391 (2003). One of the first works to explore the subcellular localization of repABC -partitioned molecules.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Cervantes-Rivera, R., Romero-Lopez, C., Berzal-Herranz, A. & Cevallos, M. A. Analysis of the mechanism of action of the antisense RNA that controls the replication of the repABC plasmid p42d. J. Bacteriol. 192, 3268–3278 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Li, P. L. & Farrand, S. K. The replicator of the nopaline-type Ti plasmid pTiC58 is a member of the repABC family and is influenced by the TraR-dependent quorum-sensing regulatory system. J. Bacteriol. 182, 179–188 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Cho, H. & Winans, S. C. VirA and VirG activate the Ti plasmid repABC operon, elevating plasmid copy number in response to wound-released chemical signals. Proc. Natl Acad. Sci. USA 102, 14843–14848 (2005). This study, together with references 65 and 32, shows that extracellular signalling cues can increase the copy number of replicons containing repABC systems.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. White, C. E. & Winans, S. C. Cell–cell communication in the plant pathogen Agrobacterium tumefaciens. Philos. Trans. R. Soc. B 362, 1135–1148 (2007).

    Article  CAS  Google Scholar 

  68. McAnulla, C., Edwards, A., Sanchez-Contreras, M., Sawers, R. G. & Downie, J. A. Quorum-sensing-regulated transcriptional initiation of plasmid transfer and replication genes in Rhizobium leguminosarum biovar viciae. Microbiology 153, 2074–2082 (2007).

    Article  CAS  PubMed  Google Scholar 

  69. He, X. et al. Quorum sensing in Rhizobium sp. strain NGR234 regulates conjugal transfer (tra) gene expression and influences growth rate. J. Bacteriol. 185, 809–822 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Casadesus, J. & Low, D. Epigenetic gene regulation in the bacterial world. Microbiol. Mol. Biol. Rev. 70, 830–856 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Marinus, M. G. & Casadesus, J. Roles of DNA adenine methylation in host–pathogen interactions: mismatch repair, transcriptional regulation, and more. FEMS Microbiol. Rev. 33, 488–503 (2009).

    Article  CAS  PubMed  Google Scholar 

  72. Bae, S. H. et al. Structure and dynamics of hemimethylated GATC sites: implications for DNA-SeqA recognition. J. Biol. Chem. 278, 45987–45993 (2003).

    Article  CAS  PubMed  Google Scholar 

  73. Guo, Q., Lu, M. & Kallenbach, N. R. Effect of hemimethylation and methylation of adenine on the structure and stability of model DNA duplexes. Biochemistry 34, 16359–16364 (1995).

    Article  CAS  PubMed  Google Scholar 

  74. Collins, M. & Myers, R. M. Alterations in DNA helix stability due to base modifications can be evaluated using denaturing gradient gel electrophoresis. J. Mol. Biol. 198, 737–744 (1987).

    Article  CAS  PubMed  Google Scholar 

  75. Katayama, T., Ozaki, S., Keyamura, K. & Fujimitsu, K. Regulation of the replication cycle: conserved and diverse regulatory systems for DnaA and oriC. Nature Rev. Microbiol. 8, 163–170 (2010).

    Article  CAS  Google Scholar 

  76. Wion, D. & Casadesus, J. N6-methyl-adenine: an epigenetic signal for DNA-protein interactions. Nature Rev. Microbiol. 4, 183–192 (2006).

    Article  CAS  Google Scholar 

  77. Shaheen, S. M., Ouimet, M. C. & Marczynski, G. T. Comparative analysis of Caulobacter chromosome replication origins. Microbiology 155, 1215–1225 (2009).

    Article  CAS  PubMed  Google Scholar 

  78. Collier, J., McAdams, H. H. & Shapiro, L. A. DNA methylation ratchet governs progression through a bacterial cell cycle. Proc. Natl Acad. Sci. USA 104, 17111–17116 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Reisenauer, A. & Shapiro, L. DNA methylation affects the cell cycle transcription of the CtrA global regulator in Caulobacter. EMBO J. 21, 4969–4977 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kahng, L. S. & Shapiro, L. The CcrM DNA methyltransferase of Agrobacterium tumefaciens is essential, and its activity is cell cycle regulated. J. Bacteriol. 183, 3065–3075 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kline, B. C. Aspects of plasmid F maintenance in Escherichia coli. Can. J. Microbiol. 34, 526–535 (1988).

    Article  CAS  PubMed  Google Scholar 

  82. Firshein, W. & Kim, P. Plasmid replication and partition in Escherichia coli: is the cell membrane the key? Mol. Microbiol. 23, 1–10 (1997).

    Article  CAS  PubMed  Google Scholar 

  83. Kolatka, K., Kubik, S., Rajewska, M. & Konieczny, I. Replication and partitioning of the broad-host-range plasmid RK2. Plasmid 64, 119–134 (2010).

    Article  CAS  PubMed  Google Scholar 

  84. Funnell, B. E. & Phillips, G. J. Plasmid Biology (American Society for Microbiology, 2004).

    Google Scholar 

  85. Nakasu, S. & Tomizawa, J. Structure of the ColE1 DNA molecule before segregation to daughter molecules. Proc. Natl Acad. Sci. USA 89, 10139–10143 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Filutowicz, M. & Rakowski, S. A. Regulatory implications of protein assemblies at the γ origin of plasmid R6K – a review. Gene 223, 195–204 (1998).

    Article  CAS  PubMed  Google Scholar 

  87. del Solar, G. & Espinosa, M. Plasmid copy number control: an ever-growing story. Mol. Microbiol. 37, 492–500 (2000). This review describes the mechanisms that regulate plasmid copy number in response to fluctuations of cis - or trans -acting elements.

    Article  CAS  PubMed  Google Scholar 

  88. Nordstrom, K. Plasmid R1—replication and its control. Plasmid 55, 1–26 (2006).

    Article  CAS  PubMed  Google Scholar 

  89. Wagner, G. Plasmids: copy number control by antisense RNAs in Biology and Significance of Plasmids: A Multi-talk Discussion of Extrachromosomal Elements in Microorganisms (ed. Clewell, D.) The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London [online] (2008).

    Google Scholar 

  90. Funnell, B. Plasmid segregation and stability in bacteria in Biology and Significance of Plasmids: A Multi-talk Discussion of Extrachromosomal Elements in Microorganisms (ed. Clewell, D.) The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London [online] (2008).

    Google Scholar 

  91. Gerdes, K., Moller-Jensen, J. & Bugge Jensen, R. Plasmid and chromosome partitioning: surprises from phylogeny. Mol. Microbiol. 37, 455–466 (2000).

    Article  CAS  PubMed  Google Scholar 

  92. Bignell, C. & Thomas, C. M. The bacterial ParA-ParB partitioning proteins. J. Biotechnol. 91, 1–34 (2001). A review that, together with reference 89, offers fundamental information on ParA–ParB systems

    Article  CAS  PubMed  Google Scholar 

  93. Ebersbach, G. & Gerdes, K. Plasmid segregation mechanisms. Annu. Rev. Genet. 39, 453–479 (2005).

    Article  CAS  PubMed  Google Scholar 

  94. Mori, H. et al. Purification and characterization of SopA and SopB proteins essential for F plasmid partitioning. J. Biol. Chem. 264, 15535–15541 (1989).

    CAS  PubMed  Google Scholar 

  95. Davis, M. A., Martin, K. A. & Austin, S. J. Biochemical activities of the ParA partition protein of the P1 plasmid. Mol. Microbiol. 6, 1141–1147 (1992).

    Article  CAS  PubMed  Google Scholar 

  96. Davey, M. J. & Funnell, B. E. The P1 plasmid partition protein ParA. A role for ATP in site-specific DNA binding. J. Biol. Chem. 269, 29908–29913 (1994).

    CAS  PubMed  Google Scholar 

  97. Breier, A. M. & Grossman, A. D. Whole-genome analysis of the chromosome partitioning and sporulation protein Spo0J (ParB) reveals spreading and origin-distal sites on the Bacillus subtilis chromosome. Mol. Microbiol. 64, 703–718 (2007).

    Article  CAS  PubMed  Google Scholar 

  98. Grigoriev, P. S. & Lobocka, M. B. Determinants of segregational stability of the linear plasmid-prophage N15 of Escherichia coli. Mol. Microbiol. 42, 355–368 (2001).

    Article  CAS  PubMed  Google Scholar 

  99. Rodionov, O., Lobocka, M. & Yarmolinsky, M. Silencing of genes flanking the P1 plasmid centromere. Science 283, 546–549 (1999).

    Article  CAS  PubMed  Google Scholar 

  100. Bingle, L. E., Macartney, D. P., Fantozzi, A., Manzoor, S. E. & Thomas, C. M. Flexibility in repression and cooperativity by KorB of broad host range IncP-1 plasmid RK2. J. Mol. Biol. 349, 302–316 (2005).

    Article  CAS  PubMed  Google Scholar 

  101. Surtees, J. A. & Funnell, B. E. The DNA binding domains of P1 ParB and the architecture of the P1 plasmid partition complex. J. Biol. Chem. 276, 12385–12394 (2001).

    Article  CAS  PubMed  Google Scholar 

  102. Schumacher, M. A. Structural biology of plasmid segregation proteins. Curr. Opin. Struct. Biol. 17, 103–109 (2007). A detailed description of plasmid 'segrosome' assembly in bacterial mitosis.

    Article  CAS  PubMed  Google Scholar 

  103. Schumacher, M. A. Structural biology of plasmid partition: uncovering the molecular mechanisms of DNA segregation. Biochem. J. 412, 1–18 (2008).

    Article  CAS  PubMed  Google Scholar 

  104. Bouet, J. Y. & Funnell, B. E. P1 ParA interacts with the P1 partition complex at parS and an ATP–ADP switch controls ParA activities. EMBO J. 18, 1415–1424 (1999). One of the first works to demonstrate the dual nature of ParA function: in autoregulation and in partitioning.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Vecchiarelli, A. G. et al. ATP control of dynamic P1 ParA–DNA interactions: a key role for the nucleoid in plasmid partition. Mol. Microbiol. 78, 78–91 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Ringgaard, S., van Zon, J., Howard, M. & Gerdes, K. Movement and equipositioning of plasmids by ParA filament disassembly. Proc. Natl Acad. Sci. USA 106, 19369–19374 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Havey, J. C., Vecchiarelli, A. G. & Funnell, B. E. ATP-regulated interactions between P1 ParA, ParB and non-specific DNA that are stabilized by the plasmid partition site, parS. Nucleic Acids Res. 40, 801–812 (2012).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The work from the author's laboratory that is described in this article was supported by a grant from the National Institute of General Medical Sciences, US National Institutes of Health (GM042893). U.M.P. acknowledges financial support from the Brazilian government through the Coordenação de Aperfeicoamento de Pessoal de Nível Superior (Capes). K.M.P. acknowledges the University of Athens (Greece) Research Committee (grant 70/4/7809).

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Correspondence to Stephen C. Winans.

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Supplementary information Table S1

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FURTHER INFORMATION

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Genbank

Glossary

Alphaproteobacteria

A group of Gram-negative, generally flagellated bacteria.

Plasmids

Semi-autonomous DNA sequences that are dispensable for bacterial growth but often confer useful new survival and colonization strategies on their bacterial hosts.

Partitioning

The distribution (or segregation) of newly replicated daughter plasmids to each of two nascent daughter cells.

Replicons

Autonomously replicating DNA molecules.

Chromids

Replicons with both plasmid- and chromosome-like features: chromids have similar GC contents to cognate primary chromosomes and carry genes that are essential for core physiology, but they use plasmid-like partitioning and replication systems. The term chromid is largely synonymous with the term secondary chromosome.

Conjugative transfer

A form of interbacterial plasmid transfer that requires contact between a donor cell and a recipient cell.

Origin of replication

The minimal DNA region that supports autonomous replication. In plasmids, this is called oriV.

ParA and ParB

Proteins that mediate the partitioning of plasmids, prophages or chromosomes to nascent daughter cells.

dnaA

A gene encoding a protein that binds to bacterial replication origins and recruits other components of the replication machinery.

Counter-transcribed RNA

A term used in plasmid biology to describe a type of antisense RNA that is synthesized from the DNA strand which is complementary to its target RNA. Like other antisense RNAs, counter-transcribed RNAs form a duplex with their targets, usually leading to degradation of both strands.

Copy number

The number of copies of a plasmid per bacterial cell; this number is generally held constant by the replication machinery.

Autorepression

The ability of a protein to repress the promoter of the gene encoding that protein.

CtrA

A transcription factor of Caulobacter crescentus that is synthesized and phosphorylated during a particular portion of the cell cycle to regulate the expression of various promoters.

VirG

A transcription factor of Agrobacterium spp. that is phosphorylated by VirA in response to plant-released phenolic compounds and activates transcription of plasmid tumour-inducing vir genes, which direct the transfer of tumorigenic DNA fragments into host cell nuclei.

Quorum sensing

A form of transcriptional regulation in bacteria. Quorum sensing systems consist of a bacterial pheromone (which accumulates at high population density), a pheromone synthase and a pheromone receptor, and they most often function to activate target genes in the presence of the pheromone.

Dam methylase

A DNA methylase that is found in enterobacteria and methylates the A residues of GATC motifs. Cells can recognize newly synthesized DNA by its lack of methylation.

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Pinto, U., Pappas, K. & Winans, S. The ABCs of plasmid replication and segregation. Nat Rev Microbiol 10, 755–765 (2012). https://doi.org/10.1038/nrmicro2882

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