1887

Abstract

Preterminal protein (pTP) is a component of the preinitiation complex which forms at the adenovirus origin of DNA replication and acts as the protein primer during DNA synthesis. In order to determine the role of various regions of the molecule a series of 18 mutations was introduced into conserved motifs of pTP which were predicted to be surface exposed, and the mutants expressed in insect cells using a baculovirus expression system. Their ability to initiate DNA replication was assessed and the effect the mutations have on the individual interactions which contribute to the formation of the pre-initiation complex was determined. Classes of mutants could be identified which were unable to bind DNA or interact with the adenovirus DNA polymerase, but one class of mutants retained these activities and yet failed to initiate DNA replication. These mutants therefore identify regions of pTP required for different aspects of adenovirus DNA replication.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-82-8-1917
2001-08-01
2020-01-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/82/8/0821917a.html?itemId=/content/journal/jgv/10.1099/0022-1317-82-8-1917&mimeType=html&fmt=ahah

References

  1. Bosher, J., Robinson, E. C. & Hay, R. T. ( 1990; ). Interactions between the adenovirus type 2 polymerase and the DNA binding domain of nuclear factor 1. New Biologist 2, 1083-1090.
    [Google Scholar]
  2. Botting, C. H. & Hay, R. T. ( 1999; ). Characterisation of the adenovirus preterminal protein and its interaction with the POU homeodomain of NFIII (Oct-1). Nucleic Acids Research 27, 2799-2805.[CrossRef]
    [Google Scholar]
  3. Challberg, M. D. & Rawlins, D. R. ( 1984; ). Template requirements for the initiation of adenovirus DNA replication. Proceedings of the National Academy of Sciences, USA 81, 100-104.[CrossRef]
    [Google Scholar]
  4. Challberg, M. D., Desiderio, S. V. & Kelly, T. J. ( 1980; ). Adenovirus DNA replication in vitro: characterisation of a protein covalently linked to nascent DNA strands. Proceedings of the National Academy of Sciences, USA 77, 5105-5109.[CrossRef]
    [Google Scholar]
  5. Chen, M., Mermod, N. & Horwitz, M. S. ( 1990; ). Protein–protein interactions between adenovirus DNA polymerase and nuclear factor-1 mediate formation of the DNA replication preinitiation complex. Journal of Biological Chemistry 265, 18634-18642.
    [Google Scholar]
  6. Cleat, P. H. & Hay, R. T. ( 1989; ). Co-operative interactions between NF-1 and the adenovirus DNA binding protein at the origin of DNA replication. EMBO Journal 8, 1841-1848.
    [Google Scholar]
  7. Coenjaerts, E. J., van Oosterhout, J. A. W. M. & van der Vliet, P. C. ( 1994; ). The Oct-1 POU domain stimulates adenovirus DNA replication by a direct interaction between the viral precursor terminal protein–DNA polymerase complex and the POU homeodomain. EMBO Journal 13, 5401-5409.
    [Google Scholar]
  8. Fredman, J. N., Pettit, S. C., Horowitz, M. S. & Engler, J. A. ( 1991; ). Linker insertion mutations in the adenovirus preterminal protein that affect DNA replication in vivo and in vitro. Journal of Virology 65, 4591-4597.
    [Google Scholar]
  9. Freimuth, P. I. & Ginsberg, H. S. ( 1986; ). Codon insertion mutants of the adenovirus terminal protein. Proceedings of the National Academy of Sciences, USA 83, 7816-7820.[CrossRef]
    [Google Scholar]
  10. Hay, R. T. & Russell, W. C. ( 1989; ). Recognition mechanisms in the synthesis of animal virus DNAs. Biochemical Journal 258, 3-16.
    [Google Scholar]
  11. King, A. J. & van der Vliet, P. C. ( 1994; ). A precursor terminal protein-trinucleotide intermediate during initiation of adenovirus DNA replication: regeneration of molecular ends in vitro by a jumping back mechanism. EMBO Journal 13, 5786-5792.
    [Google Scholar]
  12. King, A. J., Teertstra, W. R. & van der Vliet, P. C. ( 1997; ). Dissociation of the protein primer and DNA polymerase after initiation of adenovirus DNA replication. Journal of Biological Chemistry 272, 24617-24623.[CrossRef]
    [Google Scholar]
  13. Mul, Y. M., Verrijzer, C. P. & van der Vliet, P. C. ( 1990; ). Transcription factors NFI and NFIII/oct-1 function independently, employing different mechanisms to enhance adenovirus DNA replication. Journal of Virology 64, 5510-5518.
    [Google Scholar]
  14. Nagata, K., Guggenheimer, R. A. & Hurwitz, J. ( 1983; ). Specific binding of a cellular DNA replication protein to the origin of replication of adenovirus DNA. Proceedings of the National Academy of Sciences, USA 80, 4266-4270.[CrossRef]
    [Google Scholar]
  15. Parker, E. J., Botting, C. H., Webster, A. & Hay, R. T. ( 1998; ). Adenovirus DNA polymerase: domain organisation and interaction with preterminal protein. Nucleic Acids Research 26, 1240-1247.[CrossRef]
    [Google Scholar]
  16. Pettit, S. C., Horwitz, M. S. & Engler, J. A. ( 1989; ). Mutations in the precursor to the terminal protein of adenovirus serotypes 2 and 5. Journal of Virology 63, 5244-5250.
    [Google Scholar]
  17. Pronk, R. & van der Vliet, P. C. ( 1993; ). The adenovirus terminal protein influences binding of replication proteins and changes the origin structure. Nucleic Acids Research 21, 2293-2300.[CrossRef]
    [Google Scholar]
  18. Pruijn, G. J. M., Van Priel, W. & Van der Vliet, P. C. ( 1986; ). A novel sequence specific DNA binding protein from HeLa cells stimulating adenovirus DNA replication. Nature 322, 656-659.[CrossRef]
    [Google Scholar]
  19. Roovers, D. J., Overman, P. F., Chen, X. Q. & Sussenbach, J. S. ( 1991; ). Linker mutation scanning of the genes encoding the adenovirus type 5 terminal protein precursor and DNA polymerase. Virology 180, 273-284.[CrossRef]
    [Google Scholar]
  20. Roovers, D. J., van der Lee, F. M., van der Wees, J. & Sussenbach, J. S. ( 1993; ). Analysis of the adenovirus type 5 terminal protein precursor and DNA polymerase by linker insertion mutagenesis. Journal of Virology 67, 265-276.
    [Google Scholar]
  21. Rost, B. & Sander, C. ( 1993; ). Improved prediction of protein secondary structure by use of sequence profiles and neural networks. Proceedings of the National Academy of Sciences, USA 90, 7558-7562.[CrossRef]
    [Google Scholar]
  22. Schaack, J., Ho, W. Y., Tolman, S., Ullyat, E., Guo, X., Frank, N., Freimuth, P. I., Roovers, D. J. & Sussenbach, J. S. ( 1999; ). Construction and preliminary characterization of a library of ‘lethal’ preterminal protein mutant adenoviruses. Journal of Virology 73, 9599-9603.
    [Google Scholar]
  23. Van Leeuwen, H. C., Rensen, M. & van der Vliet, P. C. ( 1997; ). The Oct-1 POU homeodomain stabilizes the adenovirus preinitiation complex via a direct interaction with the priming protein and is displaced when the replication fork passes. Journal of Biological Chemistry 272, 3398-3405.[CrossRef]
    [Google Scholar]
  24. Webster, A., Leith, I. R. & Hay, R. T. ( 1994; ). Activation of the adenovirus coded protease and processing of the preterminal protein. Journal of Virology 68, 7292-7300.
    [Google Scholar]
  25. Webster, A., Leith, I. R. & Hay, R. T. ( 1997a; ). Domain organization of the adenovirus preterminal protein. Journal of Virology 71, 539-547.
    [Google Scholar]
  26. Webster, A., Leith, I. R., Nicholson, J., Hounsell, J. & Hay, R. T. ( 1997b; ). Role of preterminal protein processing in adenovirus replication. Journal of Virology 71, 6381-6389.
    [Google Scholar]
  27. Zhao, L. & Padmanabhan, R. ( 1988; ). Nuclear transport of adenovirus DNA polymerase is facilitated by interaction with preterminal protein. Cell 55, 1005-1015.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-82-8-1917
Loading
/content/journal/jgv/10.1099/0022-1317-82-8-1917
Loading

Data & Media loading...

Most cited articles

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error