Copy Mutants of the Plasmid R 1 as a Tool in Studies of Control of Plasmid Replication

  • Kurt Nordström
  • Birgitta Engberg
  • Petter Gustafsson
  • Søren Molin
  • Bernt Eric Uhlin
Conference paper
Part of the Topics in Infectious Diseases book series (TIDIS, volume 2)


Replication of bacterial chromosomes and plasmids is carefully regulated; their cellular concentration is kept constant in an exponentially growing population of bacteria /4/, /13/. Replication is controlled at the level of initiation /38/. The initiation mass (cell mass per origin) of the Escherichia coli chromosome is constant at least at growth rates above one generation per hour suggesting that initiation mass is the parameter used to control replication /10/, /36/, /38/. This is a reasonable idea since it requires measurement of a concentration, a principle often used in biochemical processes. Two main models have been proposed to explain the coupling between replication and growth, the one suggesting positive /19/, the other negative control /37/, /39/. Many experiments have been performed in order to distinguish between these two models, but almost no definitive answers have so far been obtained. Control of DNA replication differs from the control of synthesis of other cellular macromolecules in that the number of molecules that are synthesized per cell (and per cell generation) is limited; in some cases this number is only one. This particularly applies to the chromosome but also to many plasmids. on the other hand, it is absolutely necessary that the process is carefully controlled, otherwise cells lacking the DNA molecule could become abundant.


Plasmid Copy Plasmid Copy Number Plasmid Replication Chromosome Replication Newborn Cell 
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  1. 1.
    Bazaral, M., Helinski, D.R.: Replication of a bacterial plasmid and an episome in Escherichia coli. Biochemistry 9, 399–406 (1970).PubMedCrossRefGoogle Scholar
  2. 2.
    Berg, D.E.: Genes of phage A essential for Adv plasmids. Virology 62, 224–233 (1974).PubMedCrossRefGoogle Scholar
  3. 3.
    Cabello, P., Timmis, K., Cohen, S. N.: Replication control in a composite plasmid constructed by in vitro linkage of two distinct replicons. Nature (London) 259, 285–290 (1976)CrossRefGoogle Scholar
  4. 4.
    Clowes, R.C.: Molecular structure of bacterial plasmids. Bacteriol. Rev. 36, 361–405 (1972).PubMedGoogle Scholar
  5. 5.
    Collins, J., Pritchard, R. H.: Relationship between chromosome replication and F’lac episome replication in Escherichia coli. J. Mol. Biol. 78, 143–155 (1973).PubMedCrossRefGoogle Scholar
  6. 6.
    Cooper, S.: Relationship of F’lac replication and chromosome replication. Proc. Natl. Acad. Sci. U.S.A. 69, 2706–2710 (1972).PubMedCrossRefGoogle Scholar
  7. 7.
    Cooper, S., Helmstetter, C. E.: Chromosome replication and the division cycle of Escherichia coli B/r. J. Mol. Biol. 31, 519–540 (1968).PubMedCrossRefGoogle Scholar
  8. 8.
    Cress, D. E., Kline, B. C.: Isolation and characterization of Escherichia coli chromosomal mutants affecting plasmid copy number. J. Bacteriol. 125, 635–642 (1976).PubMedGoogle Scholar
  9. 9.
    Davis, D. B., Helmstetter, C. E.: Control of F’lac replication in Escherichia coli B/r. J. Bacteriol. 114, 294–299 (1973)PubMedGoogle Scholar
  10. 10.
    Donachie, W. D.: Relationship between cell size and time of initiation of DNA replication. Nature (London) 219, 1077–1079 (1968).CrossRefGoogle Scholar
  11. 11.
    Egawa, R., Hirota, Y.: Inhibition of fertility by multiple drug-resistance factor (R) in Escherichia coli K-12. Jpn. J. Genet. 37, 66–69 (1962).CrossRefGoogle Scholar
  12. 12.
    Engberg, B., Nordström, K.: Replication of the R-factor R1 in Escherichia coli K-12 at different growth rates. J. Bacteriol. 123, 179–186 (1975).PubMedGoogle Scholar
  13. 13.
    Falkow, S.: Infectious multiple drug resistance. Pion Ltd., London 1975.Google Scholar
  14. 14.
    Goebel, W.: The influence of dnaA and dnaC mutations on the initiation of plasmid DNA replication. Biochem. Biophys. Res. Commun. 51, 1000–1007 (1973).PubMedCrossRefGoogle Scholar
  15. 15.
    Goebel, W.: Replication of plasmid DNA in Escherichia coli. Proc. Soc. Gen. Microbiol. 1, 1–2 (1973).Google Scholar
  16. 16.
    Grinsted, J., Saunders, J. R., Ingram, L. C., Sykes, R. B., Richmond, M. H.: Properties of an R-factor wich originated in Pseudomonas aeruginosa 1822. J. Bacteriol. 110, 529–537 (1972).PubMedGoogle Scholar
  17. 17.
    Gustafsson, P., Nordström, K.: Random replication of the stringent plasmid R1 in Escherichia coli K-12. J. Bacteriol. 123, 443–448 (1975).PubMedGoogle Scholar
  18. 18.
    Helmstetter, C. E., Cooper, S.: DNA synthesis during the division cycle of rapidly growing Escherichia coli B/r. J. Mol. Biol. 31, 507–518 (1968).PubMedCrossRefGoogle Scholar
  19. 19.
    Jacob, F., Brenner, S., Cuzin, F.: On the regulation of DNA replication in bacteria. Cold Spring Harbor Symp. Quant. Biol. 28, 329–348 (1963).Google Scholar
  20. 20.
    Kline, B. C.: Mechanism and biosynthesis requirements for F plasmid replication in Escherichia coli. Biochemistry 13, 139–146 (1974).PubMedCrossRefGoogle Scholar
  21. 21.
    Kool, A. J., van Zeben, M. S., Nijkamp, H. J. J.: Identification of messenger ribonucleic acids and proteins synthesized by the bacteriocinogenic factor C1oDF13 in purified minicells of Escherichia coli. J. Bacteriol. 118, 213–224 (1974).PubMedGoogle Scholar
  22. 22.
    Kubitschek H.: Generation times: ancestral dependence and dependence upon cell size. Exp. Cell. Res. 43, 30–38 (1966).PubMedCrossRefGoogle Scholar
  23. 23.
    Lark, K. G., Repko, R., Hoffman, E. J.: The effect of amino acid deprivation on subsequent deoxyribonucleic acid replication. Biochim. Biophys. Acta 76, 9–24 (1963).PubMedCrossRefGoogle Scholar
  24. 24.
    Macrina, F. L., Weatherly, G. G., Curtiss, R. III: R6K plasmid replication: influence of chromosomal genotype in minicellproducing strains of Escherichia coli K-12. J. Bacteriol. 120, 1387–1400 (1974).PubMedGoogle Scholar
  25. 25.
    Matsubara, K.: Genetic structure and regulation of a replication of plasmid adv. J. Mol. Biol. 102, 427–439 (1976).PubMedCrossRefGoogle Scholar
  26. 26.
    Matsubara, K., Takeda, Y.: Role of the tof gene in the production and perpetuation of the Jdv plasmid. Mol. Gen. Genet. 142, 225–230 (1975).PubMedCrossRefGoogle Scholar
  27. 27.
    Meselson, M., Stahl, F. W.: The replication of DNA in Escherichia coli. Proc. Soc. Natl. Acad. Sci. U.S. 44, 671–682 (1958).CrossRefGoogle Scholar
  28. 28.
    Meynell, E., Datta, N.: The relation of resistance transfer factors to the F-factor (sex-factor) of Escherichia coli K-12. Genet. Res. 7, 134–140 (1966).PubMedCrossRefGoogle Scholar
  29. 29.
    Meynell, E., Datta, N.: Mutant drug-resistant factors of high transmissibility. Nature (London) 214, 885–887 (1967).CrossRefGoogle Scholar
  30. 30.
    Morris, C. F., Hashimoto, H., Mickel, S., Rownd, R.: Round of replication mutant of a drug resistance factor. J. Bacteriol. 118, 855–866 (1974).PubMedGoogle Scholar
  31. 31.
    Nordström, K.: Increased resistance to several antibiotics by one mutation in an R-factor, R1a. J. Gen. Microbiol. 66, 205–214 (1971).PubMedGoogle Scholar
  32. 32.
    Nordström, K., Eriksson-Grennberg, K.G., Boman, H.G.: Resistance of Escherichia coli to penicillins. III. AmpB, a locus affecting episomally and chromosomally mediated resistance to ampicillin and chloramphenicol. Genet. Res. 12, 157–168 (1968).PubMedCrossRefGoogle Scholar
  33. 33.
    Nordström, K., Ingram, L. C., Lundbäck, A.: Mutations in R-factors of Escherichia coli causing an increased number of R-factor copies per chromosome. J. Bacteriol. 110, 562–569 (1972).PubMedGoogle Scholar
  34. 34.
    Nordström, U. M., Engberg, B., Nordström, K.: Competition for DNA polymerase III between the chromosome and the R-factor R1. Mol. Gen. Genet. 135, 185–190 (1974).PubMedCrossRefGoogle Scholar
  35. 35.
    Perlman, D., Twose, T. M., Holland, M. J., Rownd, R. H.: Denaturation mapping of R-factor deoxyribonucleic acid. J. Bacteriol. 123, 1035–1042 (1975).PubMedGoogle Scholar
  36. 36.
    Pritchard, R. H.: Control of DNA synthesis in bacteria. Heredity 23, 472 (1968).Google Scholar
  37. 37.
    Pritchard, R. H.: Control of replication of genetic material in bacteria, 1969, 65–74. In G.E.W. Wolstenholme and M. O’Connor (ed.), Bacterial episomes and plasmids. A Ciba Foundation Symposium. J. amp; A. Churchill Ltd., London.Google Scholar
  38. 38.
    Pritchard, R. H.: On the growth and form of a bacterial cell. Philos. Trans. R. Soc. London 264, 303–336 (1974).Google Scholar
  39. 39.
    Pritchard, R. H., Barth, P. T., Collins, J.: Control of DNA synthesis in bacteria. Symp. Soc. Gen. Microbiol. 19, 263–297 (1969).Google Scholar
  40. 40.
    Pritchard, R. H., Chandler, M. G., Collins, J.: Independence of F replication and chromosome replication in Escherichia coli. Mol. Gen. Genet. 138, 143–155 (1975).PubMedCrossRefGoogle Scholar
  41. 41.
    Pritchard, R. H., Lark, K. L.: Induction of replication by thimine starvation at tha chromosome origin in Escherichia coli. J. Mol. Biol. 9, 288–307 (1964).PubMedCrossRefGoogle Scholar
  42. 42.
    Reanney, D.: Extrachromosomal elements as possible agents of adaptation and development. Bacteriol. Revs. 40, 552–590 (1976).Google Scholar
  43. 43.
    Rownd, R.: Replication of a bacterial episome under relaxed control. J. Mol. Biol. 44, 387–402 (1969).PubMedCrossRefGoogle Scholar
  44. 44.
    Schaechter, M., Williamson, J. P., Hood, J. R.,Jr., Koch, A. C.: Growth, cell and nuclear divisions in some bacteria. J. Gen. Microbiol. 29, 421–434 (1962).PubMedGoogle Scholar
  45. 45.
    Sompayrac, L., and O. MaalOe: Autorepressor model for control of DNA replication. Nature (London) New. Biol. 241, 133–135 (1973).Google Scholar
  46. 46.
    Thompson, R., Broda, P.: DNA polymerase III and the replication of F and Co1VBtrp in Escherichia coli. Mol. Gen. Genet. 127, 255–258 (1973).PubMedCrossRefGoogle Scholar
  47. 47.
    Timmis, K., Winkler, U.: Gene dosage studies with pleiotropic mutants of Serratia marcescens superactive in the synthesis of marcescin A and certain other exocellular proteins. Mol. Gen. Genet. 124, 207–217 (1973).PubMedCrossRefGoogle Scholar
  48. 48.
    Uhlin, B. E., Nordström, K.: Plasmid incompatibility and control of replication: Copy mutants of the R-factor R1 in Escherichia coli K-12. J. Bacteriol. 124, 641–649 (1975).PubMedGoogle Scholar
  49. 49.
    Zeuthen, J., Pato, M. L.: Replication of the F’lac sex factor in the cell cycle of Escherichia coli. Mol. Gen. Genet. 111, 242–255 (1971).PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1977

Authors and Affiliations

  • Kurt Nordström
  • Birgitta Engberg
    • 1
  • Petter Gustafsson
  • Søren Molin
  • Bernt Eric Uhlin
  1. 1.Department of MicrobiologyUniversity of UmeåSweden

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