Is the Nuclear Membrane Involved in DNA Replication?

  • David E. Comings
  • Tadashi A. Okada


In 1963 Jacob, Brenner and Cuzin proposed the replicon concept for bacterial DNA and on the basis of some later modifications suggested that the replicating point was attached to the bacterial cell membrane. Since basic mechanisms in prokaryotes have a certain probability of being similar to basic mechanisms in eukaryotes, I was interested in, examining the question of whether membrane attachment played a role in DNA replication in mammalian cells. We were primarily interested in whether DNA replication might be initiated at the nuclear membrane since a few autoradiographic studies had already suggested that replication could take place throughout the nucleus, implying that in mammalian cells the replication point did not always remain at the membrane. These previous studies, however, were mostly with 30 minute pulse labels. To examine this question human amnion cells were synchronized first with excess thymidine for 24 hours. The excess thymidine was then washed out and the cells allowed to pass through the S period for 10 hours and then further synchronized by exposure to amethopterin for 14 hours. The cultures were then exposed to tritiated thymidine for 10 minutes and after appropriate fixation electron microscope autoradiography performed.


Nuclear Membrane Synaptonemal Complex Tritiated Thymidine Chinese Hamster Cell Bacterial Cell Membrane 
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  1. 1.
    Amaldi, F., Carnevali, F., Leoni, L. and Mariotti, D. The replicon origins in Chinese hamster cell DNA: I. Labeling procedure and preliminary observations. Exp. Cell Res. 74: 367–374, 1972.PubMedCrossRefGoogle Scholar
  2. 2.
    Comings, D. E. The rationale for an ordered arrangement of chromatin in the interphase nucleus. Am. J. Human Genet. 20: 440–460, 1968.Google Scholar
  3. 3.
    Comings, D. E. The structure and function of chromatin, in Advances in Human Genetics, vol. 3, pp 237–431, Harris and Hirschhorn (eds), Plenum Press, New York, 1972.Google Scholar
  4. 4.
    Comings, D. E. and Kakefuda, T. Initiation of DNA replication at the nuclear membrane in human cells. J. Mol. Biol. 33: 225–229, 1968.PubMedCrossRefGoogle Scholar
  5. 5.
    Comings, D. E. and Kakefuda, T. Association of nuclear membrane fragments with metaphase and anaphase chromosomes as observed by whole mount electron microscopy. Exp. Cell Res. 63: 62–68, 1970a.PubMedCrossRefGoogle Scholar
  6. 6.
    Comings, D. E. and Okada, T. A. Association of chromatin fibers with the annuli of the nuclear membrane. Exp. Cell Res. 62: 293–302, 1970b.PubMedCrossRefGoogle Scholar
  7. 7.
    Comings, D. E. and Okada, T. A. Whole mount electron microscopy of meiotic chromosomes and the synaptonemal complex. Chromosoma 30: 269–286, 1970c.PubMedCrossRefGoogle Scholar
  8. 8.
    Comings, D. E. and Okada, T. A. Mechanism of chromosome pairing during meiosis. Nature 227: 451–456, 1970d.PubMedCrossRefGoogle Scholar
  9. 9.
    Comings, D. E. and Okada, T. A. Condensation of chromosomes onto the nuclear membrane during prophase. Exp. Cell Res. 63: 471–473, 1971.CrossRefGoogle Scholar
  10. 10.
    Comings, D. E. and Okada, T. A. DNA replication and the nuclear membrane. J. Mol. Biol. 75: (in press) 1973.Google Scholar
  11. 11.
    DuPraw, E. J. The organization of nuclei and chromosomes in honeybee embryonic cells. Proc. Nat. Acad. Sci. USA 53: 161–168, 1965.PubMedCrossRefGoogle Scholar
  12. 12.
    Heneen, W. K. and Nichols, W. W. Non-random arrangement of metaphase chromosomes in cultured cells of the Indian deer, Muntiacus muntjak. Cytogenetics 11: 153–164, 1972.PubMedCrossRefGoogle Scholar
  13. 13.
    Jacob, F., Brenner, S. and Cuzin, F. On the regulation of DNA replication. Cold Spring Harbor Symposium on Quant. Biol. 28.: 329–348, 1963.Google Scholar
  14. 14.
    Moses, M. J. Structure and function of the synaptonemal complex. Genetics 61: 41–51, 1969.PubMedGoogle Scholar
  15. 15.
    Ockey, C. H. Distribution of DNA replicator sites in mammalian nuclei. II. Effects of prolonged inhibition of DNA synthesis. Exp. Cell Res. 70: 203–213, 1972.PubMedCrossRefGoogle Scholar
  16. 16.
    Williams, C. A. and Ockey, C. H. Distribution of DNA replicator sites in mammalian nuclei after different methods of cell synchronization. Exp. Cell Res. 63: 365–372, 1970.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1974

Authors and Affiliations

  • David E. Comings
    • 1
  • Tadashi A. Okada
    • 1
  1. 1.Department of Medical GeneticsCity of Hope National Medical CenterDuarteUSA

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