1887

Abstract

We have previously shown that most Rous sarcoma proviruses in Rat-1 cells are simple insertions, at apparently random sites, and are not transcribed. A small minority of simple insertions are transcribed and these show a bias to insertion at sites closely 3′ to presumptive cellular CG-rich islands. However, most transcribed proviruses are complex, typified by contiguous duplications of proviral DNA 5′ to a complete proviral unit. The cellular sites of these complex insertions are unknown and their structure and significance incompletely documented. We report here more extensive analyses of proviral duplications, with the following findings. The 5′ duplications predominantly involve proviral regions known to contain enhancer functions, substantiating earlier data. The cellular insertion sites are not biased to CG-rich loci at the level displayed by simple transcribed proviruses. The detailed structure of two duplications, and partial analysis of several others, strongly favours their genesis by illegitimate template transfer at reverse transcription, followed by self-recombination. These findings show that aberrant reverse transcription can generate duplications that dispense with the need for an expressed provirus to be integrated at a favourable cellular site.

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1992-12-01
2024-04-19
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References

  1. Arrigo S., Yun M., Beemon K. 1987; cis-Acting regulatory elements within gag genes of avian retroviruses. Molecular and Cellular Biology 7:388–397
    [Google Scholar]
  2. Cullen B. R., Kyle B., Ju G. 1985; Functional analysis of the transcription control region located within the avian retroviral long terminal repeat. Molecular and Cellular Biology 5:438–447
    [Google Scholar]
  3. Falcone G., Provenzano C., Alema S., Tato F. 1992; Transformation of NIH3T3 cells by Rous sarcoma virus occurs with high efficiency in the absence of proviral rearrangements or amplification. Oncogene 7:1913–1920
    [Google Scholar]
  4. Fincham V. J., Wyke J. A. 1991; Differences between cellular integration sites of transcribed and nontranscribed Rous sarcoma proviruses. Journal of Virology 65:461–463
    [Google Scholar]
  5. Gillespie D. A. F., Hart K. A., Wyke J. A. 1985; Rearrangements or viral and cellular DNA are often associated with expression of Rous sarcoma virus in rat cells. Cell 41:279–287
    [Google Scholar]
  6. Green A. R., Searle S., Gillespie D. A. F., Bissell M., Wyke J. A. 1986; Expression of integrated Rous sarcoma viruses: DNA rearrangements 5′ to the provirus are common in transformed rat cells but not seen in infected but untransformed cells. EMBO Journal 5:707–711
    [Google Scholar]
  7. Levantis P., Gillespie D. A. F., Hart K., Bissell M. J., Wyke J. A. 1986; Control of expression of an integrated Rous sarcoma provirus in rat cells. Role of 5′ genomic duplications reveals unexpected patterns of gene transcription and its regulation. Journal of Virology 57:907–916
    [Google Scholar]
  8. Lindsay S., Bird A. P. 1987; Use of restriction enzymes to detect potential gene sequences in mammalian DNA. Nature, London 327:336–338
    [Google Scholar]
  9. Luciw P. A., Bishop J. M., Varmus H. E., Capecchi M. R. 1983; Location and function of retroviral and SV40 sequences that enhance biochemical transformation after microinjection of DNA. Cell 33:705–716
    [Google Scholar]
  10. Nordheim A., Rich A. 1983; Negatively supercoiled simian virus 40 DNA contains Z-DNA segments within transcriptional enhancer sequences. Nature, London 303:674–678
    [Google Scholar]
  11. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: A Laboratory Manual 2nd edn New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  12. Schwartz D. E., Tizard R., Gilbert W. 1983; Nucleotide sequence of Rous sarcoma virus. Cell 32:853–869
    [Google Scholar]
  13. Shoemaker C., Goff S., Gilboa E., Paskind M., Mitra S. W., Baltimore D. 1980; Structure of a cloned circular Moloney murine leukemia virus DNA molecule containing an inverted segment: implications for retrovirus integration. Proceedings of the National Academy of Sciences, U.S.A. 77:3932–3936
    [Google Scholar]
  14. Varmus H. E., Swanstrom R. 1984; Replication of retroviruses. In RNA Tumor Viruses vol 1 pp. 369–512 Edited by Weiss R., Teich N., Varmus H., Coffin J. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
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