Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1995 Dec 15;14(24):6218–6228. doi: 10.1002/j.1460-2075.1995.tb00312.x

Co-operative interaction between the initiator E1 and the transcriptional activator E2 is required for replicator specific DNA replication of bovine papillomavirus in vivo and in vitro.

J Sedman 1, A Stenlund 1
PMCID: PMC394746  PMID: 8557041

Abstract

The E1 polypeptide from bovine papillomavirus binds to the origin of replication (ori) and possesses the activities attributed to initiator proteins. E1 is also the only viral protein required for replication in a cell-free replication system. Replication in vivo, however, absolutely requires in addition the viral transcription factor E2. We demonstrate that the basis for this distinction between in vitro and in vivo requirements is the limited sequence specificity of the E1 protein. E1 and E2, which bind the ori individually with low sequence specificity, together bind with greatly increased sequence specificity. This combinatorial effect provides a function for the involvement of transcriptional activation domains in replication and suggests common mechanisms of action for transcription factors in both transcription and replication. It also provides a possible explanation for the differential specificity that is observed for auxiliary transcription factors in vivo.

Full text

PDF
6218

Images in this article

6219Image
on p.6219
6220Image
on p.6220
6221Image
on p.6221
6222Image
on p.6222
6223Image
on p.6223
6224Image
on p.6224
6225Image
on p.6225
6226Image
on p.6226

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baru M., Shlissel M., Manor H. The yeast GAL4 protein transactivates the polyomavirus origin of DNA replication in mouse cells. J Virol. 1991 Jul;65(7):3496–3503. doi: 10.1128/jvi.65.7.3496-3503.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bennett-Cook E. R., Hassell J. A. Activation of polyomavirus DNA replication by yeast GAL4 is dependent on its transcriptional activation domains. EMBO J. 1991 Apr;10(4):959–969. doi: 10.1002/j.1460-2075.1991.tb08030.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bosher J., Robinson E. C., Hay R. T. Interactions between the adenovirus type 2 DNA polymerase and the DNA binding domain of nuclear factor I. New Biol. 1990 Dec;2(12):1083–1090. [PubMed] [Google Scholar]
  4. Chen M., Mermod N., Horwitz M. S. Protein-protein interactions between adenovirus DNA polymerase and nuclear factor I mediate formation of the DNA replication preinitiation complex. J Biol Chem. 1990 Oct 25;265(30):18634–18642. [PubMed] [Google Scholar]
  5. Cheng L. Z., Workman J. L., Kingston R. E., Kelly T. J. Regulation of DNA replication in vitro by the transcriptional activation domain of GAL4-VP16. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):589–593. doi: 10.1073/pnas.89.2.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cheng L., Kelly T. J. Transcriptional activator nuclear factor I stimulates the replication of SV40 minichromosomes in vivo and in vitro. Cell. 1989 Nov 3;59(3):541–551. doi: 10.1016/0092-8674(89)90037-8. [DOI] [PubMed] [Google Scholar]
  7. Chiang C. M., Ustav M., Stenlund A., Ho T. F., Broker T. R., Chow L. T. Viral E1 and E2 proteins support replication of homologous and heterologous papillomaviral origins. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5799–5803. doi: 10.1073/pnas.89.13.5799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DePamphilis M. L. Eukaryotic DNA replication: anatomy of an origin. Annu Rev Biochem. 1993;62:29–63. doi: 10.1146/annurev.bi.62.070193.000333. [DOI] [PubMed] [Google Scholar]
  9. Gillette T. G., Lusky M., Borowiec J. A. Induction of structural changes in the bovine papillomavirus type 1 origin of replication by the viral E1 and E2 proteins. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8846–8850. doi: 10.1073/pnas.91.19.8846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gopalakrishnan V., Khan S. A. E1 protein of human papillomavirus type 1a is sufficient for initiation of viral DNA replication. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9597–9601. doi: 10.1073/pnas.91.20.9597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Guo Z. S., DePamphilis M. L. Specific transcription factors stimulate simian virus 40 and polyomavirus origins of DNA replication. Mol Cell Biol. 1992 Jun;12(6):2514–2524. doi: 10.1128/mcb.12.6.2514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. He Z., Brinton B. T., Greenblatt J., Hassell J. A., Ingles C. J. The transactivator proteins VP16 and GAL4 bind replication factor A. Cell. 1993 Jun 18;73(6):1223–1232. doi: 10.1016/0092-8674(93)90650-f. [DOI] [PubMed] [Google Scholar]
  13. Hoang A. T., Wang W., Gralla J. D. The replication activation potential of selected RNA polymerase II promoter elements at the simian virus 40 origin. Mol Cell Biol. 1992 Jul;12(7):3087–3093. doi: 10.1128/mcb.12.7.3087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Holt S. E., Schuller G., Wilson V. G. DNA binding specificity of the bovine papillomavirus E1 protein is determined by sequences contained within an 18-base-pair inverted repeat element at the origin of replication. J Virol. 1994 Feb;68(2):1094–1102. doi: 10.1128/jvi.68.2.1094-1102.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Johnson A. D., Pabo C. O., Sauer R. T. Bacteriophage lambda repressor and cro protein: interactions with operator DNA. Methods Enzymol. 1980;65(1):839–856. doi: 10.1016/s0076-6879(80)65078-2. [DOI] [PubMed] [Google Scholar]
  16. Johnson A. D., Poteete A. R., Lauer G., Sauer R. T., Ackers G. K., Ptashne M. lambda Repressor and cro--components of an efficient molecular switch. Nature. 1981 Nov 19;294(5838):217–223. doi: 10.1038/294217a0. [DOI] [PubMed] [Google Scholar]
  17. Johnson A., Meyer B. J., Ptashne M. Mechanism of action of the cro protein of bacteriophage lambda. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1783–1787. doi: 10.1073/pnas.75.4.1783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jones K. A., Yamamoto K. R., Tjian R. Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro. Cell. 1985 Sep;42(2):559–572. doi: 10.1016/0092-8674(85)90113-8. [DOI] [PubMed] [Google Scholar]
  19. Kuo S. R., Liu J. S., Broker T. R., Chow L. T. Cell-free replication of the human papillomavirus DNA with homologous viral E1 and E2 proteins and human cell extracts. J Biol Chem. 1994 Sep 30;269(39):24058–24065. [PubMed] [Google Scholar]
  20. Le Moal M. A., Yaniv M., Thierry F. The bovine papillomavirus type 1 (BPV1) replication protein E1 modulates transcriptional activation by interacting with BPV1 E2. J Virol. 1994 Feb;68(2):1085–1093. doi: 10.1128/jvi.68.2.1085-1093.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Li R., Botchan M. R. Acidic transcription factors alleviate nucleosome-mediated repression of DNA replication of bovine papillomavirus type 1. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7051–7055. doi: 10.1073/pnas.91.15.7051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Li R., Botchan M. R. The acidic transcriptional activation domains of VP16 and p53 bind the cellular replication protein A and stimulate in vitro BPV-1 DNA replication. Cell. 1993 Jun 18;73(6):1207–1221. doi: 10.1016/0092-8674(93)90649-b. [DOI] [PubMed] [Google Scholar]
  23. Li R., Knight J., Bream G., Stenlund A., Botchan M. Specific recognition nucleotides and their DNA context determine the affinity of E2 protein for 17 binding sites in the BPV-1 genome. Genes Dev. 1989 Apr;3(4):510–526. doi: 10.1101/gad.3.4.510. [DOI] [PubMed] [Google Scholar]
  24. Lu J. Z., Sun Y. N., Rose R. C., Bonnez W., McCance D. J. Two E2 binding sites (E2BS) alone or one E2BS plus an A/T-rich region are minimal requirements for the replication of the human papillomavirus type 11 origin. J Virol. 1993 Dec;67(12):7131–7139. doi: 10.1128/jvi.67.12.7131-7139.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lusky M., Fontane E. Formation of the complex of bovine papillomavirus E1 and E2 proteins is modulated by E2 phosphorylation and depends upon sequences within the carboxyl terminus of E1. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6363–6367. doi: 10.1073/pnas.88.14.6363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lusky M., Hurwitz J., Seo Y. S. The bovine papillomavirus E2 protein modulates the assembly of but is not stably maintained in a replication-competent multimeric E1-replication origin complex. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8895–8899. doi: 10.1073/pnas.91.19.8895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. McBride A. A., Romanczuk H., Howley P. M. The papillomavirus E2 regulatory proteins. J Biol Chem. 1991 Oct 5;266(28):18411–18414. [PubMed] [Google Scholar]
  28. Mohr I. J., Clark R., Sun S., Androphy E. J., MacPherson P., Botchan M. R. Targeting the E1 replication protein to the papillomavirus origin of replication by complex formation with the E2 transactivator. Science. 1990 Dec 21;250(4988):1694–1699. doi: 10.1126/science.2176744. [DOI] [PubMed] [Google Scholar]
  29. Mul Y. M., Van der Vliet P. C. Nuclear factor I enhances adenovirus DNA replication by increasing the stability of a preinitiation complex. EMBO J. 1992 Feb;11(2):751–760. doi: 10.1002/j.1460-2075.1992.tb05108.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mul Y. M., Verrijzer C. P., van der Vliet P. C. Transcription factors NFI and NFIII/oct-1 function independently, employing different mechanisms to enhance adenovirus DNA replication. J Virol. 1990 Nov;64(11):5510–5518. doi: 10.1128/jvi.64.11.5510-5518.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Müller F., Seo Y. S., Hurwitz J. Replication of bovine papillomavirus type 1 origin-containing DNA in crude extracts and with purified proteins. J Biol Chem. 1994 Jun 24;269(25):17086–17094. [PubMed] [Google Scholar]
  32. Park P., Copeland W., Yang L., Wang T., Botchan M. R., Mohr I. J. The cellular DNA polymerase alpha-primase is required for papillomavirus DNA replication and associates with the viral E1 helicase. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8700–8704. doi: 10.1073/pnas.91.18.8700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Russell J., Botchan M. R. cis-Acting components of human papillomavirus (HPV) DNA replication: linker substitution analysis of the HPV type 11 origin. J Virol. 1995 Feb;69(2):651–660. doi: 10.1128/jvi.69.2.651-660.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Seo Y. S., Müller F., Lusky M., Gibbs E., Kim H. Y., Phillips B., Hurwitz J. Bovine papilloma virus (BPV)-encoded E2 protein enhances binding of E1 protein to the BPV replication origin. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2865–2869. doi: 10.1073/pnas.90.7.2865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Seo Y. S., Müller F., Lusky M., Hurwitz J. Bovine papilloma virus (BPV)-encoded E1 protein contains multiple activities required for BPV DNA replication. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):702–706. doi: 10.1073/pnas.90.2.702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Smith D. L., Johnson A. D. A molecular mechanism for combinatorial control in yeast: MCM1 protein sets the spacing and orientation of the homeodomains of an alpha 2 dimer. Cell. 1992 Jan 10;68(1):133–142. doi: 10.1016/0092-8674(92)90212-u. [DOI] [PubMed] [Google Scholar]
  37. Spalholz B. A., McBride A. A., Sarafi T., Quintero J. Binding of bovine papillomavirus E1 to the origin is not sufficient for DNA replication. Virology. 1993 Mar;193(1):201–212. doi: 10.1006/viro.1993.1116. [DOI] [PubMed] [Google Scholar]
  38. Sverdrup F., Khan S. A. Two E2 binding sites alone are sufficient to function as the minimal origin of replication of human papillomavirus type 18 DNA. J Virol. 1995 Feb;69(2):1319–1323. doi: 10.1128/jvi.69.2.1319-1323.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Ustav E., Ustav M., Szymanski P., Stenlund A. The bovine papillomavirus origin of replication requires a binding site for the E2 transcriptional activator. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):898–902. doi: 10.1073/pnas.90.3.898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ustav M., Stenlund A. Transient replication of BPV-1 requires two viral polypeptides encoded by the E1 and E2 open reading frames. EMBO J. 1991 Feb;10(2):449–457. doi: 10.1002/j.1460-2075.1991.tb07967.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Ustav M., Ustav E., Szymanski P., Stenlund A. Identification of the origin of replication of bovine papillomavirus and characterization of the viral origin recognition factor E1. EMBO J. 1991 Dec;10(13):4321–4329. doi: 10.1002/j.1460-2075.1991.tb05010.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wilson V. G., Ludes-Meyers J. A bovine papillomavirus E1-related protein binds specifically to bovine papillomavirus DNA. J Virol. 1991 Oct;65(10):5314–5322. doi: 10.1128/jvi.65.10.5314-5322.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Yang L., Li R., Mohr I. J., Clark R., Botchan M. R. Activation of BPV-1 replication in vitro by the transcription factor E2. Nature. 1991 Oct 17;353(6345):628–632. doi: 10.1038/353628a0. [DOI] [PubMed] [Google Scholar]
  44. Yang L., Mohr I., Fouts E., Lim D. A., Nohaile M., Botchan M. The E1 protein of bovine papilloma virus 1 is an ATP-dependent DNA helicase. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5086–5090. doi: 10.1073/pnas.90.11.5086. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES