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On the Mechanism of Recombination Between Adenoviral and Cellular DNAs: The Structure of Junction Sites

Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 109)

Abstract

The integration of adenovirus DNA into host cell DNA was studied in considerable detail in abortively and productively infected cells, as well as in transformed and tumor cells induced by human adenoviruses (for a review see Doerfler 1982). More than 70 different adenovirus-transformed cell lines and tumor cell lines from adenovirus-induced tumors exhibited non-indentical patterns of viral DNA insertion into the host genome. In this context harmster, mouse, and rat systems were investigated From these studies, there was no evidence for highly specific sites of viral DNA inserion into the cellular genome as judged by the results of Southern blotting analyses. Of course, intergratiom patterns in established transformed or tumor cell lines could have been modified by postintergrational alterations, such as rearrangements, amplifications, or partial deletions, and thus possible specificities could have been obscured. On the other hand, in several in stances it could be demonstrated that the cellular nucleotide sequences at the sites of junction were not altered (Gahlmann et al. 1982; Stabel and Doerfler 1982; Gahlmann and Doerfler? 1983). Obvious sequence specificities at the sites of insertion have so far not been found in the adenovirus, SV40, or polyoma virus system.

Keywords

Adenovirus Type Junction Site Baby Hamster Kidney Cell Junction Fragment Cellular Sequence 
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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References

  1. Benton WD, Davis RW (1977) Screening Agt recombinant clones by hybridization to single plaques in situ. Science 196: 180–182PubMedCrossRefGoogle Scholar
  2. Bos JL, Polder JL, Bernards R, Schrier PI, Van den Elsen PJ, Van der Eb AJ, Van Ormondt H (1981) The 2.2 kb Elb mRNA of human Adl2 and Ad5 codes for two tumor antigens starting at different AUG triplets. Cell 27: 121–131PubMedCrossRefGoogle Scholar
  3. Botchan M, Topp W, Sambrook J (1976) The arrangement of simian virus 40 sequences in the DNA of transformed cells. Cell 9: 269–287PubMedCrossRefGoogle Scholar
  4. Burger H, Doerfler W (1974) Intracellular forms of adenovirus DNA. III. Integration of the DNA of adenovirus type 2 into host DNA in productively infected cells. J Virol 13: 975–992PubMedGoogle Scholar
  5. Cook JL, Lewis AM Jr (1979) Host response to adenovirus 2–transformed hamster embryo cells. Cancer Res 39: 1455–1461PubMedGoogle Scholar
  6. Deuring R, Doerfler W (1983) Proof or recombination between viral and cellular genomes in human KB cells productively infected by adenovirus type 12: structure of the junction site in a symmetric recombinant ( SYREC ). Gene 24Google Scholar
  7. Deuring R, Klotz G, Doerfler W (1981 a) An unusual symmetric recombinant between adenovirus type 12 DNA and human cell DNA. Proc Natl Acad Sci USA 78: 3142–3146Google Scholar
  8. Deuring R, Winterhoff U, Tamanoi F, Stabel S, Doerfler W (1981b) Site of linkage between adenovirus type 12 and cell DNAs in hamster tumor line CLAC3. Nature 293: 81–84PubMedCrossRefGoogle Scholar
  9. Doerfler W (1968) The fate of the DNA of adenovirus type 12 in baby hamster kidney cells. Proc Natl Acad Sci USA 60: 636–643PubMedCrossRefGoogle Scholar
  10. Doerfler W (1969) Nonproductive infection of baby hamster kidney cells (BHK21) with adenovirus type 12. Virology 38: 587–606PubMedCrossRefGoogle Scholar
  11. Doerfler W (1970) Integration of the deoxyribonucleic acid of adenovirus type 12 into deoxyribonucleic acid of baby hamster kidney cells. J Virol 6: 652–666PubMedGoogle Scholar
  12. Doerfler W (1982) Uptake, fixation and expression of foreign DNA in mammalian cells: The organization of integrated adenovirus sequences. Curr Top Microbiol Immunol 101: 127–194PubMedGoogle Scholar
  13. Doerfler W, Lundholm U, Hirsch-Kauffmann M (1972) Intracellular forms of adenovirus deoxyribonucleic acid. I. Evidence for a deoxyribonucleic acid-protein complex in baby hamster kidney cells infected with adenovirus type 12. J Virol 9: 297–308PubMedGoogle Scholar
  14. Doerfler W, Lundholm U, Rensing U, Philipson L (1973) Intracellular forms of adenovirus DNA. II. Isolation in dye buoyant density gradients of a DNA-RNA complex from KB cells infected with adenovirus type 2. J Virol 12: 793–807PubMedGoogle Scholar
  15. Eick D, Doerfler W (1982) Integrated adenovirus type 12 DNA in the transformed hamster cell line T637: Sequence arrangements at the termini of viral DNA and mode of amplification. J Virol 42: 317–321Google Scholar
  16. Eick D, Stabel S, Doerfler W (1980) Revertants of adenovirus type 12-transformed hamster cell line T637 as tools in the analysis of integration patterns. J Virol 36: 41–49PubMedGoogle Scholar
  17. Eick D, Kemper B, Doerfler W (1983) Excision of amplified viral DNA at palindromic sequences from the adenovirus type 12-transformed hamster cell line T637. The EMBO J 2: 1981–1986Google Scholar
  18. Esche H, Siegmann B (1982) Expression of early viral gene products in adenovirus type 12-infected and — transformed cells. J Gen Virol 60: 99–113PubMedCrossRefGoogle Scholar
  19. Esche H, Schilling R, Doerfler W (1979) In vitro translation of adenovirus type 12-specific mRNA isolated from infected and transformed cells. J Virol 30: 21–31PubMedGoogle Scholar
  20. Fanning E, Doerfler W (1976) Intracellular forms of adenovirus DNA. V. Viral DNA sequences in hamster cells abortively infected and transformed with human adenovirus type 12. J Virol 20: 373–383PubMedGoogle Scholar
  21. Gahlmann R, Doerfler W (1983) Integration of viral DNA into the genome of the adenovirus type 2-transformed hamster cell line HE5 without loss or alteration of cellular nucleotides. Nucleic Acids Res 11: 7347–7361PubMedCrossRefGoogle Scholar
  22. Gahlmann R, Leisten R, Vardimon L, Doerfler W (1982) Patch homologies and the integration of adenovirus DNA in mammalian cells. EMBO J 1: 1101–1104PubMedGoogle Scholar
  23. Gallimore PH (1974) Interactions of adenovirus type 2 with rat embryo cells: Permissiveness, transformation and in vitro characteristics of adenovirus-transformed rat embryo cells. J Gen Virol 25: 263–273PubMedCrossRefGoogle Scholar
  24. Gingeras TR, Sciaky D, Gelinas RE, Bing-Dong J, Yen CE, Kelly MM, Bullock PA, Parsons BL, O’Neill KE, Roberts RJ (1982) Nucleotide sequences from the adenovirus 2 genome. J Biol Chem 257: 13475–13491PubMedGoogle Scholar
  25. Groneberg J, Doerfler W (1979) Revertants of adenovirus type 12-transformed hamster cells have lost part of the viral genomes. Int J Cancer 24: 67–74PubMedCrossRefGoogle Scholar
  26. Groneberg J, Chardonnet Y, Doerfler W (1977) Integrated viral sequences in adenovirus type 12-transformed hamster cells. Cell 10: 101–111PubMedCrossRefGoogle Scholar
  27. Groneberg J, Sutter D, Soboll H, Doerfler W (1978) Morphological revertants of adenovirus type 12-transformed hamster cells. J Gen Virol 40: 635–645PubMedCrossRefGoogle Scholar
  28. Gutai MW, Nathans D (1978) Evolutionary variants of simian virus 40: cellular DNA sequences and sequences at recombinant joints of substituted variants. J Mol Biol 126: 275–288PubMedCrossRefGoogle Scholar
  29. Hammarskjöld ML, Winberg G (1980) Encapsidation of adenovirus 16 DNA is directed by a small DNA sequence at the left end of the genome. Cell 20: 787–795PubMedCrossRefGoogle Scholar
  30. Hammarskjöld ML, Winberg G (1983) Further characterization of the packaging sequence of Ad16 (Abstr). Gulbenkian Workshop on the Molecular Biology of Adenoviruses, Sintra, PortugalGoogle Scholar
  31. Hayday A, Ruley HE, Fried M (1982) Structural and biological analysis of integrated polyoma virus DNA and its adjacent host sequences cloned from transformed rat cells. J Virol 44: 67–77PubMedGoogle Scholar
  32. Hohn B (1979) In vitro packaging of X and cosmid DNA. Methods Enzymol 68: 299–309PubMedCrossRefGoogle Scholar
  33. Hohn B, Murray K (1977) Packaging recombinant DNA molecules into bacteriophage X particles in vitro. Proc Natl Acad Sci USA 74: 3259–3263PubMedCrossRefGoogle Scholar
  34. Holliday R (1964) A mechanism for gene conversion in fungi. Genet Res 5: 282–304CrossRefGoogle Scholar
  35. Ibelgaufts H, Doerfler W, Scheidtmann KH, Wechsler W (1980) Adenovirus type 12–induced rat tumor cells of neuroepithelial origin: Persistence and expression of the viral genome. J Virol 33: 423–437Google Scholar
  36. Johansson K, Persson H, Lewis AM, Pettersson U, Tibbetts C, Philipson L (1978) Viral DNA sequences and gene products in hamster cells transformed by adenovirus type 2. J Virol 27: 628–639PubMedGoogle Scholar
  37. Kemper B, Garabett M (1981) Studies on T4 head maturation. 1. Purification and characterization of gene-49-controlled endonuclease. Eur J Biochem 115: 123–131PubMedCrossRefGoogle Scholar
  38. Ketner G, Kelly TJ Jr (1976) Integrated simian virus 40 sequences in transformed cell DNA: analysis using restriction endonucleases. Proc Natl Acad Sci USA 73: 1102–1106PubMedCrossRefGoogle Scholar
  39. Kimura T, Sawada Y, Shinawawa M, Shimizu Y, Shiroki K, Shimojo H, Sugisaki H, Takanami M, Uemizu Y, Fujinaga K (1981) Nucleotide sequence of the transforming early region Elb of adenovirus type 12 DNA: structure and gene organization, and comparison with those of adenovirus type 5 DNA. Nucleic Acids Res 9: 6571–6589PubMedCrossRefGoogle Scholar
  40. Kuhlmann I, Doerfler W (1982) Shifts in the extent and patterns of DNA methylation upon explantation and subcultivation of adenovirus type 12-induced hamster tumor cells. Virology 118: 169–180PubMedCrossRefGoogle Scholar
  41. Kuhlmann I, Achten S, Rudolph R, Doerfler W (1982) Tumor induction by human adenovirus type 12 in hamsters: loss of the viral genome from adenovirus type 12-induced tumor cells is compatible with tumor formation. EMBO J 1: 79–86PubMedGoogle Scholar
  42. Kruczek I, Doerfler W (1982) The unmethylated state of the promoter/leader and 5’ regions of integrated adenovirus genes correlates with gene expression. EMBO J 1: 409–414PubMedGoogle Scholar
  43. Landy A, Ross W (1977) Viral integration and excision: structure of the lambda att sites. Science 197: 1147–1160PubMedCrossRefGoogle Scholar
  44. Majors JE, Varmus HE (1981) Nucleotide sequence at host-proviral junctions for mouse mammary tumor virus. Nature 289: 253–258PubMedCrossRefGoogle Scholar
  45. Maxam AM, Gilbert W (1977) A new method for sequencing DNA. Proc Natl Acad Sci USA 74: 560–564PubMedCrossRefGoogle Scholar
  46. Maxam AM, Gilbert W (1980) Sequencing end-labeled DNA with base–specific chemical cleavages. Methods Enzymol 65: 499–560PubMedCrossRefGoogle Scholar
  47. Mendelsohn E, Baran N, Neer A, Manor H (1982) Integration site of polyoma virus DNA in the inducible LPT line of polyoma-transformed rat cells. J Virol 41: 192–209PubMedGoogle Scholar
  48. Mizuuchi K, Kemper B, Hays J, Weisberg RA (1982) T4 endonuclease VII cleaves Holliday structures. Cell 29: 357–365PubMedCrossRefGoogle Scholar
  49. Ortin J, Scheidtmann KH, Greenberg R, Westphal M, Doerfler W (1976) Transcription of the genome of adenovirus type 12. III. Maps of stable RNA from productively infected human cells and abortively infected and transformed hamster cells. J Virol 20: 355–372Google Scholar
  50. Roberts RJ, Sciaky D, Gelinas RE, Jiang B-D, Yen CE, Kelly MM, Bullock PA, Parsons KE, O’Neill KE, Gingeras TR (1982) Information content of adenovirus-2 genome. Cold Spring Harbor Symp Quant Biol 47: 1025–1037Google Scholar
  51. Robinson AJ, Younghusband HB, Bellet AJD (1973) A circular DNA-protein-complex from adenoviruses. Virology 56: 54–69PubMedCrossRefGoogle Scholar
  52. Ross W, Landy A (1983) Patterns of I int recognition in the regions of strand exchange. Cell 33: 261–272PubMedCrossRefGoogle Scholar
  53. Ruben M, Bacchetti S, Graham F (1983) Covalently closed circles of adenovirus 5 DNA. Nature 301: 172–174PubMedCrossRefGoogle Scholar
  54. Sambrook J, Botchan M, Gallimore P, Ozanne B, Pettersson U, Williams J, Sharp PA (1974) Viral DNA sequences in cells transformed by simian virus 40, adenovirus type 2 and adenovirus type 5. Cold Spring Harbor Symp Quant Biol 39: 615–632Google Scholar
  55. Sambrook J, Greene R, Stringer J, Mitchison T, Hu S-L, Botchan M (1979) Analysis of the sites of integration of viral DNA sequences in rat cells transformed by adenovirus 2 or SV40. Cold Spring Harbor Symp Quant Biol 44: 569–584Google Scholar
  56. Sawada Y, Fujinaga K (1980) Mapping of adenovirus 12 mRNAs transcribed from the transforming region. J Virol 36: 639–651PubMedGoogle Scholar
  57. Schick J, Baczko K, Fanning E, Groneberg J, Burger H, Doerfler W (1976) Intracellular forms of adenovirus DNA: Integrated form of adenovirus DNA appears early in productive infection. Proc Natl Acad Sci USA 73: 1043–1047Google Scholar
  58. Schirm S, Doerfler W (1981) Expression of viral DNA in adenovirus type 12-transformed cells, in tumor cells, and in revertants. J Virol 39: 694–702PubMedGoogle Scholar
  59. Sharp PA, Gallimore PH, Flint SJ (1974) Mapping of adenovirus 2 RNA sequences in lytically infected cells and transformed cell lines. Cold Spring Harbor Symp Quant Biol 39: 457–474Google Scholar
  60. Shimizu Y, Yoshida K, Ren C-S, Fujinaga K, Rajagopalan S, Chinnadurai G (1983) Hinf family: a novel repeated DNA family of the human genome. Nature 302: 587–590PubMedCrossRefGoogle Scholar
  61. Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98: 503–517PubMedCrossRefGoogle Scholar
  62. Stabel S, Doerfler W (1982) Nucleotide sequence at the site of junction between adenovirus type 12 DNA and repetitive hamster cell DNA in transformed cell line CLAC1. Nucleic Acids Res 10: 8007–8023PubMedCrossRefGoogle Scholar
  63. Stabel S, Doerfler W, Friis RR (1980) Integration sites of adenovirus type 12 DNA in transformed hamster cells and hamster tumor cells. J Virol 36: 22–40PubMedGoogle Scholar
  64. Stringer JR (1981) Integrated simian virus 40 DNA: Nucleotide sequences at cell-virus recombinant junctions. J Virol 38: 671–679PubMedGoogle Scholar
  65. Stringer JR (1982) DNA sequence homology and chromosomal deletion at a site of SV40 DNA integration. Nature 296: 363–366PubMedCrossRefGoogle Scholar
  66. Starzinski-Powitz A, Schulz M, Esche H, Mukai N, Doerfler W (1982) The adenovirus type 12 mouse-cell system: permissivity and analysis of integration patterns of viral DNA in tumor cells. EMBO J 1: 493–497PubMedGoogle Scholar
  67. Sugisaki H, Sugimoto K, Takanami M, Shiroki K, Saito I, Shimojo H, Sawada Y, Uemizu Y, Uesugi S, Fujinaga K (1980) Structure and gene organization in the transforming Hindlll-G fragment of Adl2. Cell 20: 777–786PubMedCrossRefGoogle Scholar
  68. Sutcliffe JG (1978) Complete nucleotide sequence of the Escherichia coli plasmid pBR322. Cold Spring Harbor Symp Quant Biol 43: 77–90Google Scholar
  69. Sutter D, Doerfler W (1979) Methylation of integrated viral DNA sequences in hamster cells transformed by adenovirus 12. Cold Spring Harbor Symp Quant Biol 44: 565–568Google Scholar
  70. Sutter D, Doerfler W (1980) Methylation of integrated adenovirus type 12 DNA sequences in transformed cells is inversely correlated with viral gene expression. Proc Natl Acad Sci USA 77: 253–256PubMedCrossRefGoogle Scholar
  71. Sutter D, Westphal M, Doerfler W (1978) Patterns of integration of viral DNA sequences in the genomes of adenovirus type 12-transformed hamster cells. Cell 14: 569–585PubMedCrossRefGoogle Scholar
  72. Tikchonenko TI (to be published) Molecular biology of SI6 (SA7) and some other simian adenoviruses. In: Doerfler W (ed) The molecular biology of adenoviruses 2. Curr Top Microbiol Immunol 110Google Scholar
  73. Tiemeier D, Enquist L, Leder P (1976) Improved derivative of a phage X EK2 vector for cloning recombinant DNA. Nature 263: 526–527CrossRefGoogle Scholar
  74. Tolun A, Alestrom P, Pettersson U (1979) Sequenced of inverted terminal repetitions from different adenoviruses: demonstration of Φ conserved sequences and homology between SA 7 termini and SV40 DNA. Cell 17: 705–713PubMedCrossRefGoogle Scholar
  75. Tyndall C, Younghusband HB, Bellet AJD (1978) Some adenovirus DNA is associated with the DNA of permissive cells during productive or restricted growth. J Virol 25: 1–10PubMedGoogle Scholar
  76. Vardimon L, Doerfler W (1981) Patterns of integration of viral DNA in adenovirus type 2-transformed hamster cells. J Mol Biol 147: 227–246PubMedCrossRefGoogle Scholar
  77. Visser L, Van Maarschalkerweerd MW, Rozijn TH, Wassenaar ADC, Reemst AMCB, Sussenbach JS (1979) Viral DNA sequences in adenovirus-transformed cells. Cold Spring Harbor Symp Quant Biol 44: 541–550Google Scholar
  78. Visser L, Reemst ACMB, Van Mansfeld ADM, Rozijn TH (1982) Nucleotide sequence analysis of the linked left and right hand terminal regions of adenovirus type 5 DNA present in the transformed rat cell line 5RK20. Nucleic Acids Res 10: 2189–2198PubMedCrossRefGoogle Scholar
  79. Westin G, Visser L, Zabielski J, Van Mansfeld ADM, Pettersson U, Rozijn TH (1982) Sequence organization of a viral DNA insertion present in the adenovirus type-5-transformed hamster line BHK268-C31. Gene 17: 263–270PubMedCrossRefGoogle Scholar
  80. Wilson JH, Berget PB, Pipas JM (1982) Somatic cells efficiently join unrelated DNA segments end-to-end. Mol Cell Biol 2: 1258–1269PubMedGoogle Scholar
  81. Yasue H, Ishibashi M (1982) The oncogenicity of avian adenoviruses. III. In situ hybridization of tumor line cells localized a large number of a virocellular sequence in few chromosomes. Virology 116: 99–115Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1983

Authors and Affiliations

  1. 1.Institute of GeneticsUniversity of CologneCologne 41Germany

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