, Volume 25, Issue 4, pp 265–297 | Cite as

The internal order of the interphase nucleus

  • F. Vogel
  • T. M. Schroeder
Original Investigations


This paper has two parts. The first one is theoretical, whereas in the second, some experimenteal results are reported.

Part 1: Theoretical Considerations. Comings' considerations on an ordered arrangement of chromatin in the interphase nucleus are used as a basis for further investigations and calculations in order to establish a preliminary model of the interphase nucleus. Information on the amount of DNA of a diploid human nucleus, on the degree of spiralization of chromatin threads found in electron microscopy, and measurements of salivary gland chromosomes was used to estimate the lengths of the entire interphase chromosomes. The number of fixing points-pores—was indirectly calculated proposing a model of an internal order of the chromatin threads. This number was found in concord with a direct calculation of the number of pores in the nuclear membrane based on results from electron microscopy.

Part 2: Experimental Results and Discussion. In the second part of this study, an approach was made as to how to arrange chromosomes and chromosome segments in their proximity to each other. Results of cytogenetic studies of newborn babies and abortions, of cells from patients with Bloom's syndrome and Fanconi's anemia and normal cells treated with Mitomycin C and Trenimon, are thought to be informative under certain suppositions for the problem, which chromosome or chromosome parts are situated in proximity to each other. The symmetrical and equal interchanges seen, for example, in Bloom's syndrome are an indication of somatic pairing during the time of reunion. Therefore, the unequal interchanges in the same syndrome in which different chromosomes are involved should give evidence for proximity of nonhomologous chromosomes. Arguments for and against a temporal and spacial hypothesis for somatic pairing are discussed. The differing frequencies of chromosomes involved in Robertsonian translocations in man are informative for proximities of satellite regions at the nucleolus. Nucleolus and sex chromatin could be used as fixed points in a model of the interphase nucleus in which finally the absolute localization of the chromosomes will be discovered. The discussion points out promising methods for further investigations on the subject and mentions problems which could be attacked if the approach described here leads to a model of internal order in the interphase nucleus.


Mitomycin Interphase Nucleus Robertsonian Translocation Spacial Hypothesis Internal Order 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Beermann, W.: Riesenchromosomen. In: Protoplasmatologia. Handbuch der Protoplasmaforschung, Bd. VI D. Wien: Springer 1962Google Scholar
  2. Beermann, W.: Chromosomeres and genes. Results and problems in cell differentiation 4, 1–33 (1972)CrossRefGoogle Scholar
  3. Bochkov, N. P., Pätau, K., Therman, E.: Karyotypical analysis of irradiated human cells. Genetica 5, 108–115 (1969)Google Scholar
  4. Bochkov, N. P., Lopukhin, Y. M., Kuleshov, N. P., Kovalchuk, L. V.: Cytogenetic study of patients with ataxia-teleangiectasia. Humangenetik 24, 115–128 (1974)PubMedGoogle Scholar
  5. Britten, R. J., Davidson, E. H.: Gene regulation for higher cells: A theory. Science 165, 349–357 (1969)CrossRefGoogle Scholar
  6. Brody, S.: Chromosomal DNA synthesis in cultured diploid human fibroblasts. Diss. (Ph. D. Thesis) Wisconsin 1969Google Scholar
  7. Cairns, J.: The chromosome of Escherichia coli. Cold Spring Harbor Symposium. Quant. Biol. 28, 43 (1963)CrossRefGoogle Scholar
  8. Chiarelli, B.: Bands or chromomeres: a functional interpretation of banding and speculation about a model of nucleous and chromosome organization in the Eukaryots. Mamm. News Letters 15, 15–16 (1974)Google Scholar
  9. Cleaver, J. E.: Interphase replication of DNA and the cell cycle, In: Thymidine metabolism and cell kinetics (eds. A. Neuberger and E. L. Tatum), pp. 126–127. Amsterdam: North Holland 1967Google Scholar
  10. Cohen, M. M., Shaw, M. W.: Effects of mitomycin C on human chromosomes. J. Cell. Biol. 23, 386–395 (1964)CrossRefGoogle Scholar
  11. Cohen, M. M., Enis, P., Pfeifer, C. G.: An investigation of somatic pairing in the muntjak. Cytogenetics 11, 145–152 (1972)CrossRefGoogle Scholar
  12. Comings, D. E.: The duration of replication of the inactive X-Chromosome in humans based on the persistence of the heterochromatic sex chromatin body during DNA synthesis. Cytogenetics 6, 20–37 (1967)CrossRefGoogle Scholar
  13. Comings, D. E.: The rationale for an ordered arrangement of chromatin in the interphase nucleus. Amer. J. Hum. Genet. 20, 440–460 (1968)PubMedGoogle Scholar
  14. Comings, D. E.: The structure and function of chromatin. In: Advances in human genetics 3 (eds. H. Harris and K. Hirschhorn), p. 237–431. New York-London: Plenum Press 1972CrossRefGoogle Scholar
  15. Comings, D. E.: That is break. In: Chromosomes and cancer (ed. J. German), pp. 95–134. New York: J. Wiley 1974Google Scholar
  16. Comings, D. E., Kakefuda, T.: Initiation of DNA replication at the nuclear membrane in human cells. J. molec. Biol. 33, 225–229 (1968)CrossRefGoogle Scholar
  17. Comings, D. E., Okada, T. A.: Association of chromatin fibers with the annuli of the nuclear membrane. Exp. Cell Res. 62, 293–302 (1970a)CrossRefGoogle Scholar
  18. Comings, D. E., Okada, T. A.: Association of nuclear membrane fragments with metaphase and anaphase chromosomes as observed by whole mount electron microscopy. Exp. Cell Res. 63, 62–68 (1970b)CrossRefGoogle Scholar
  19. DuPraw, E. J., Bahr, G. F.: The arrangement of DNA in human chromosomes, as investigated by quantitative electron microscopy. Acta cytol. (Philad.) 13, 188 (1969)Google Scholar
  20. Galperin, H.: Relative positions of homologous chromosomes or groups in male and female metaphase figures. Humangenetik 7, 265–274 (1969)PubMedGoogle Scholar
  21. German, J.: Cytogenetical Evidence for crossing over in vitro in human lymphoid cells. Science 144, 298–301 (1964)CrossRefGoogle Scholar
  22. German, J., Archibald, R., Bloom, D.: Chromosomal breakage in a rare and probably genetically determined syndrome of man. Science 148, 506–507 (1965)CrossRefGoogle Scholar
  23. Grummt, F.: Interphasekern. In: Molekulare Biologie der Zelle (Hrsg. H. Bielka) S. 647–663. Jena: Fischer 1973Google Scholar
  24. Grundmann, E.: Allgemeine Cytologie. Stuttgart: Thieme 1964Google Scholar
  25. Hamerton, J.: Human cytogenetics. New York-London: Academic Press 1971Google Scholar
  26. Heneen, W. K., Nichols, W. W.: Nonrandom arrangement of metaphase chromosomes in cultured cells of the Indian deer, Muntiacus muntjak. Cytogenetics 11, 153–164 (1972)CrossRefGoogle Scholar
  27. Hienz, H. A.: Chromosomenfibel. Stuttgart: Thieme 1971Google Scholar
  28. Jacob, F., Brenner, A., Cuzin, F.: On the regulation of DNA replication. Cold Spring Harbor Symposium., Quant. Biol. 28, 329–348 (1963)CrossRefGoogle Scholar
  29. Jacob, F., Ryter, A., Cuzin, F.: On the association between DNA and membrane in bacteria. Proc. Roy. Soc. Med. B-164, 267–278 (1966)CrossRefGoogle Scholar
  30. Jaffray, J. Y., Geneix, A.: Interchromosomal fibers: Human ultrastructural study by a recent technique Humangenetik 25, 119–126 (1974)PubMedGoogle Scholar
  31. Koskull, H. von, Aula, P.: Nonrandom distribution of chromosome breaks in Fanconi's anaemia. Cytogenet. Cell Genet. 12, 423–434 (1973)CrossRefGoogle Scholar
  32. Kumar, S., Natarajan, A. T.: Kinetics of two-break chromosome exchanges and the spatial arrangement of chromosome strands in interphase nucleus. Nature (Lond.) 209, 796–797 (1966)CrossRefGoogle Scholar
  33. Lampert, F.: Attachment of human chromatin fibers to the nuclear membrane, as seen by electron microscopy. Humangenetik 13, 285–295 (1971)PubMedGoogle Scholar
  34. Metz, C. W.: Chromosome studies on the Diptera. II. The paired association of chromosomes in the Diptera, and its significance. J. exp. Zool. 21, 213–279 (1916)CrossRefGoogle Scholar
  35. Milner, G. R.: Nuclear ultrastructure of the transforming lymphocyte during inhibition of deoxyribonucleic acid synthesis with hydroxyurea. J. Cell Sci. 4, 583 (1969a)PubMedGoogle Scholar
  36. Milner, G. R.: Nuclear morphology and the ultrastructural localization of deoxyribonucleic acid synthesis during interphase. J. Cell. Sci. 4, 569 (1969b)PubMedGoogle Scholar
  37. Nichols, W. W., Bradt, C., Dwight, S., Bowne, W.: Somatic pairing in Dipteran cells in culture. Cytogenetics 11, 46–52 (1972)CrossRefGoogle Scholar
  38. Panitz, R., Rieger, R.: Chromosomen der Eukaryoten. In: Molekulare Biologie der Zelle. (ed. H. Bielka), 2. Aufl., pp. 591–646. Jena: Fischer 1973Google Scholar
  39. Paris Conference (1971): Standardization in human cytogenetics. Birth Defects, Original Article Series. Vol. VIII, No. 7, 1972. The National FoundationGoogle Scholar
  40. Rao, R. N., Natarajan, A. T.: Somatic association in relation to chemically induced chromosome aberrations in Vicia faba. Genetics 57, 821–825 (1967)PubMedPubMedCentralGoogle Scholar
  41. Rao, R. N., Johnson, R. T.: Cell fusion and its application for studies on the regulation of the cell cycle — Chapter 3, 75–126. In: Methods in Cell Physiology (ed. D. M. Rescott), Vol. V. London-New York: Academic Press 1972Google Scholar
  42. Schroeder, T. M.: Chromosomenanalysen bei haematologischen und seltenen erblichen Krankheiten. Diagnostik 5, 494–497 (1972)Google Scholar
  43. Schroeder, T. M.: Die spontane Chromosomeninstabilität bei den seltenen Erbkrankheiten: Fanconi-Anämie und Bloom-Syndrom. Deutsche med. Wschr. 98, 2213–2215 (1973)CrossRefGoogle Scholar
  44. Schroeder, T. M., Anschütz, F., Knopp, A.: Spontane Chromosomenaberrationen bei familiärer Panmyelopathie. Humangenetik 1, 194–196 (1964)PubMedGoogle Scholar
  45. Schroeder, T. M.: Relationship between chromosomal instability and leukemia. In: Modern trends in human leukemia (eds. R. Neth, R. C. Gallo, S. Siegelman, F. Stohlman Jr.). München: J. F. Lehmann 1974Google Scholar
  46. Schroeder, T. M., Kurth, R.: Spontaneous chromosomal breakage and high incidence of leukemia in inherited disease. Blood 87, 96–112 (1971)Google Scholar
  47. Schroeder, T. M., Passarge, E.: Spontaneous chromosomal instability. Humangenetik 17, 276 (1973)PubMedGoogle Scholar
  48. Schroeder, T. M., Drings, P.: Verlaufsbeobachtungen einer Fanconi Anämie bei einem Erwachsenen. Verh. dtsch. Ges. innere Med. 29, 477–481 (1973)Google Scholar
  49. Schroeder, T. M., German, J.: A comparative study of the pattern of chromosomal instability in Fanconi's anemia and Down's syndrome. IVth Int. Congr. of Human. Genet. Paris 1971. Excerpta Medica (Amst.) 233, 161 (1971)Google Scholar
  50. Schroeder, T. M., German, J.: Bloom syndrome and Fanconi anemia: Demonstration of two distinctive patterns of chromosome distribution and rearrangement. Humangenetik 25, 299–306 (1974)CrossRefGoogle Scholar
  51. Shaw, M. W., Cohen, M. M.: Chromosome exchanges in human leukocytes induced by mitomycin C. Genetics 51, No. 2 (1965)Google Scholar
  52. Spaeter, M., Schwarzfischer, H. G. Die Anordnung der Chromosomen innerhalb des Zellkernes. Proc. 6. Vers. Anat. Ges. Kiel 1974 (in press)Google Scholar
  53. Stern, C.: Somatic crossing over and segregation in Drosophila melanogaster. Genetics 21, 625–630 (1936)PubMedPubMedCentralGoogle Scholar
  54. Vogel, F.: Eine vorläufige Abschätzung der Anzahl der menschlichen Gene. Z. menschl. Vererb.- u. Konstitut.-Lehre 37, 291 (1964)Google Scholar
  55. Vogel, F.: Does the human X chromosome show evidence for clustering of genes with related functions? J. Génét. hum. 17, 475–478 (1969)PubMedGoogle Scholar
  56. Vogel, F.: Non-Randomness of base replacement in point mutation. J. Mol. Evol. 1, 334–367 (1972)CrossRefGoogle Scholar
  57. Williams, C. A., Ockey, C. H.: Distribution of DNA replicator sites in mammalian nuclei after different methods of cell synchronization. Exp. Cell. Res. 63, 365 (1970)CrossRefGoogle Scholar
  58. Wolf, U.: Personal communication (1974)Google Scholar

Copyright information

© Springer-Verlag 1974

Authors and Affiliations

  • F. Vogel
    • 1
  • T. M. Schroeder
    • 1
  1. 1.Institut für Anthropologie und HumangenetikUniversität HeidelbergHeidelbergGermany

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