Abstract
DNA replication from the plasmid origin of replication of Epstein-Barr virus requires one viral protein, EBNA1. This protein also acts as a transcriptional activator. Mutational analyses of EBNA1 have led to the conclusion that it supports transcription and DNA replication similarly. Such analyses have not probed the DNA-binding domain of EBNA1. To test whether domains of EBNA1 specifically required for either transcription or replication lie within its DNA-binding domain, we constructed a functional transcriptional activator by placing the EBNA1 DNA-binding domain in the context of the activation domains of the estrogen receptor. This hybrid protein did not support DNA replication, which indicates that the DNA-binding domain does not contain a replication-specific domain that can function along with heterologous transcriptional activating domains.
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- Adams A., Pozos T. C., Purvey H. V. Replication of latent Epstein-Barr virus genomes in normal and malignant lymphoid cells. Int J Cancer. 1989 Sep 15;44(3):560–564. doi: 10.1002/ijc.2910440331. [DOI] [PubMed] [Google Scholar]
- Adams A. Replication of latent Epstein-Barr virus genomes in Raji cells. J Virol. 1987 May;61(5):1743–1746. doi: 10.1128/jvi.61.5.1743-1746.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ambinder R. F., Mullen M. A., Chang Y. N., Hayward G. S., Hayward S. D. Functional domains of Epstein-Barr virus nuclear antigen EBNA-1. J Virol. 1991 Mar;65(3):1466–1478. doi: 10.1128/jvi.65.3.1466-1478.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
- Chittenden T., Lupton S., Levine A. J. Functional limits of oriP, the Epstein-Barr virus plasmid origin of replication. J Virol. 1989 Jul;63(7):3016–3025. doi: 10.1128/jvi.63.7.3016-3025.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DePamphilis M. L. Transcriptional elements as components of eukaryotic origins of DNA replication. Cell. 1988 Mar 11;52(5):635–638. doi: 10.1016/0092-8674(88)90398-4. [DOI] [PubMed] [Google Scholar]
- Gahn T. A., Schildkraut C. L. The Epstein-Barr virus origin of plasmid replication, oriP, contains both the initiation and termination sites of DNA replication. Cell. 1989 Aug 11;58(3):527–535. doi: 10.1016/0092-8674(89)90433-9. [DOI] [PubMed] [Google Scholar]
- Gritz L., Davies J. Plasmid-encoded hygromycin B resistance: the sequence of hygromycin B phosphotransferase gene and its expression in Escherichia coli and Saccharomyces cerevisiae. Gene. 1983 Nov;25(2-3):179–188. doi: 10.1016/0378-1119(83)90223-8. [DOI] [PubMed] [Google Scholar]
- Inoue N., Harada S., Honma T., Kitamura T., Yanagi K. The domain of Epstein-Barr virus nuclear antigen 1 essential for binding to oriP region has a sequence fitted for the hypothetical basic-helix-loop-helix structure. Virology. 1991 May;182(1):84–93. doi: 10.1016/0042-6822(91)90651-q. [DOI] [PubMed] [Google Scholar]
- Kumar V., Green S., Stack G., Berry M., Jin J. R., Chambon P. Functional domains of the human estrogen receptor. Cell. 1987 Dec 24;51(6):941–951. doi: 10.1016/0092-8674(87)90581-2. [DOI] [PubMed] [Google Scholar]
- Kumar V., Green S., Staub A., Chambon P. Localisation of the oestradiol-binding and putative DNA-binding domains of the human oestrogen receptor. EMBO J. 1986 Sep;5(9):2231–2236. doi: 10.1002/j.1460-2075.1986.tb04489.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lupton S., Levine A. J. Mapping genetic elements of Epstein-Barr virus that facilitate extrachromosomal persistence of Epstein-Barr virus-derived plasmids in human cells. Mol Cell Biol. 1985 Oct;5(10):2533–2542. doi: 10.1128/mcb.5.10.2533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Polvino-Bodnar M., Kiso J., Schaffer P. A. Mutational analysis of Epstein-Barr virus nuclear antigen 1 (EBNA 1). Nucleic Acids Res. 1988 Apr 25;16(8):3415–3435. doi: 10.1093/nar/16.8.3415. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rawlins D. R., Milman G., Hayward S. D., Hayward G. S. Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region. Cell. 1985 Oct;42(3):859–868. doi: 10.1016/0092-8674(85)90282-x. [DOI] [PubMed] [Google Scholar]
- Reisman D., Sugden B. trans activation of an Epstein-Barr viral transcriptional enhancer by the Epstein-Barr viral nuclear antigen 1. Mol Cell Biol. 1986 Nov;6(11):3838–3846. doi: 10.1128/mcb.6.11.3838. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reisman D., Yates J., Sugden B. A putative origin of replication of plasmids derived from Epstein-Barr virus is composed of two cis-acting components. Mol Cell Biol. 1985 Aug;5(8):1822–1832. doi: 10.1128/mcb.5.8.1822. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sternås L., Middleton T., Sugden B. The average number of molecules of Epstein-Barr nuclear antigen 1 per cell does not correlate with the average number of Epstein-Barr virus (EBV) DNA molecules per cell among different clones of EBV-immortalized cells. J Virol. 1990 May;64(5):2407–2410. doi: 10.1128/jvi.64.5.2407-2410.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sugden B., Warren N. A promoter of Epstein-Barr virus that can function during latent infection can be transactivated by EBNA-1, a viral protein required for viral DNA replication during latent infection. J Virol. 1989 Jun;63(6):2644–2649. doi: 10.1128/jvi.63.6.2644-2649.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomsen D. R., Stenberg R. M., Goins W. F., Stinski M. F. Promoter-regulatory region of the major immediate early gene of human cytomegalovirus. Proc Natl Acad Sci U S A. 1984 Feb;81(3):659–663. doi: 10.1073/pnas.81.3.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wysokenski D. A., Yates J. L. Multiple EBNA1-binding sites are required to form an EBNA1-dependent enhancer and to activate a minimal replicative origin within oriP of Epstein-Barr virus. J Virol. 1989 Jun;63(6):2657–2666. doi: 10.1128/jvi.63.6.2657-2666.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yates J. L., Guan N. Epstein-Barr virus-derived plasmids replicate only once per cell cycle and are not amplified after entry into cells. J Virol. 1991 Jan;65(1):483–488. doi: 10.1128/jvi.65.1.483-488.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yates J. L., Warren N., Sugden B. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. 1985 Feb 28-Mar 6Nature. 313(6005):812–815. doi: 10.1038/313812a0. [DOI] [PubMed] [Google Scholar]