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. 1998 Jan 15;26(2):631–637. doi: 10.1093/nar/26.2.631

Human RPA (hSSB) interacts with EBNA1, the latent origin binding protein of Epstein-Barr virus.

D Zhang 1, L Frappier 1, E Gibbs 1, J Hurwitz 1, M O'Donnell 1
PMCID: PMC147273  PMID: 9421526

Abstract

RPA is the replicative single-strand DNA (ssDNA) binding protein of eukaryotic chromosomes. This report shows that human RPA interacts with EBNA1, the latent origin binding protein of Epstein-Barr virus (EBV). RPA binds to EBNA1 both in solution, and when EBNA1 is bound to the EBV origin. RPA is a heterotrimer, and the main contact with EBNA1 is formed through the 70 kDa subunit of RPA, the subunit which binds to ssDNA. We propose that this interaction between RPA and EBNA1 is an early step in activation of the latent origin of EBV.

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Selected References

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  1. 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]
  2. 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]
  3. Ambinder R. F., Shah W. A., Rawlins D. R., Hayward G. S., Hayward S. D. Definition of the sequence requirements for binding of the EBNA-1 protein to its palindromic target sites in Epstein-Barr virus DNA. J Virol. 1990 May;64(5):2369–2379. doi: 10.1128/jvi.64.5.2369-2379.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brill S. J., Stillman B. Replication factor-A from Saccharomyces cerevisiae is encoded by three essential genes coordinately expressed at S phase. Genes Dev. 1991 Sep;5(9):1589–1600. doi: 10.1101/gad.5.9.1589. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Din S., Brill S. J., Fairman M. P., Stillman B. Cell-cycle-regulated phosphorylation of DNA replication factor A from human and yeast cells. Genes Dev. 1990 Jun;4(6):968–977. doi: 10.1101/gad.4.6.968. [DOI] [PubMed] [Google Scholar]
  7. Dornreiter I., Erdile L. F., Gilbert I. U., von Winkler D., Kelly T. J., Fanning E. Interaction of DNA polymerase alpha-primase with cellular replication protein A and SV40 T antigen. EMBO J. 1992 Feb;11(2):769–776. doi: 10.1002/j.1460-2075.1992.tb05110.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Erdile L. F., Heyer W. D., Kolodner R., Kelly T. J. Characterization of a cDNA encoding the 70-kDa single-stranded DNA-binding subunit of human replication protein A and the role of the protein in DNA replication. J Biol Chem. 1991 Jun 25;266(18):12090–12098. [PubMed] [Google Scholar]
  9. Erdile L. F., Wold M. S., Kelly T. J. The primary structure of the 32-kDa subunit of human replication protein A. J Biol Chem. 1990 Feb 25;265(6):3177–3182. [PubMed] [Google Scholar]
  10. Fairman M. P., Stillman B. Cellular factors required for multiple stages of SV40 DNA replication in vitro. EMBO J. 1988 Apr;7(4):1211–1218. doi: 10.1002/j.1460-2075.1988.tb02933.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Frappier L., O'Donnell M. EBNA1 distorts oriP, the Epstein-Barr virus latent replication origin. J Virol. 1992 Mar;66(3):1786–1790. doi: 10.1128/jvi.66.3.1786-1790.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Frappier L., O'Donnell M. Epstein-Barr nuclear antigen 1 mediates a DNA loop within the latent replication origin of Epstein-Barr virus. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10875–10879. doi: 10.1073/pnas.88.23.10875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Frappier L., O'Donnell M. Overproduction, purification, and characterization of EBNA1, the origin binding protein of Epstein-Barr virus. J Biol Chem. 1991 Apr 25;266(12):7819–7826. [PubMed] [Google Scholar]
  14. 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]
  15. Granzow R., Reed R. Interactions in the fourth dimension. Biotechnology (N Y) 1992 Apr;10(4):390–393. doi: 10.1038/nbt0492-390. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Hearing J., Mülhaupt Y., Harper S. Interaction of Epstein-Barr virus nuclear antigen 1 with the viral latent origin of replication. J Virol. 1992 Feb;66(2):694–705. doi: 10.1128/jvi.66.2.694-705.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Henricksen L. A., Umbricht C. B., Wold M. S. Recombinant replication protein A: expression, complex formation, and functional characterization. J Biol Chem. 1994 Apr 15;269(15):11121–11132. [PubMed] [Google Scholar]
  19. Hsieh D. J., Camiolo S. M., Yates J. L. Constitutive binding of EBNA1 protein to the Epstein-Barr virus replication origin, oriP, with distortion of DNA structure during latent infection. EMBO J. 1993 Dec 15;12(13):4933–4944. doi: 10.1002/j.1460-2075.1993.tb06187.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kenny M. K., Schlegel U., Furneaux H., Hurwitz J. The role of human single-stranded DNA binding protein and its individual subunits in simian virus 40 DNA replication. J Biol Chem. 1990 May 5;265(13):7693–7700. [PubMed] [Google Scholar]
  21. Kong X. P., Onrust R., O'Donnell M., Kuriyan J. Three-dimensional structure of the beta subunit of E. coli DNA polymerase III holoenzyme: a sliding DNA clamp. Cell. 1992 May 1;69(3):425–437. doi: 10.1016/0092-8674(92)90445-i. [DOI] [PubMed] [Google Scholar]
  22. Lee S. H., Eki T., Hurwitz J. Synthesis of DNA containing the simian virus 40 origin of replication by the combined action of DNA polymerases alpha and delta. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7361–7365. doi: 10.1073/pnas.86.19.7361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lee S. H., Kwong A. D., Pan Z. Q., Hurwitz J. Studies on the activator 1 protein complex, an accessory factor for proliferating cell nuclear antigen-dependent DNA polymerase delta. J Biol Chem. 1991 Jan 5;266(1):594–602. [PubMed] [Google Scholar]
  24. Li L., Lu X., Peterson C. A., Legerski R. J. An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair. Mol Cell Biol. 1995 Oct;15(10):5396–5402. doi: 10.1128/mcb.15.10.5396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Philipova D., Mullen J. R., Maniar H. S., Lu J., Gu C., Brill S. J. A hierarchy of SSB protomers in replication protein A. Genes Dev. 1996 Sep 1;10(17):2222–2233. doi: 10.1101/gad.10.17.2222. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. Stigger E., Dean F. B., Hurwitz J., Lee S. H. Reconstitution of functional human single-stranded DNA-binding protein from individual subunits expressed by recombinant baculoviruses. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):579–583. doi: 10.1073/pnas.91.2.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Stukenberg P. T., Turner J., O'Donnell M. An explanation for lagging strand replication: polymerase hopping among DNA sliding clamps. Cell. 1994 Sep 9;78(5):877–887. doi: 10.1016/s0092-8674(94)90662-9. [DOI] [PubMed] [Google Scholar]
  31. Su W., Middleton T., Sugden B., Echols H. DNA looping between the origin of replication of Epstein-Barr virus and its enhancer site: stabilization of an origin complex with Epstein-Barr nuclear antigen 1. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10870–10874. doi: 10.1073/pnas.88.23.10870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tong X., Wang F., Thut C. J., Kieff E. The Epstein-Barr virus nuclear protein 2 acidic domain can interact with TFIIB, TAF40, and RPA70 but not with TATA-binding protein. J Virol. 1995 Jan;69(1):585–588. doi: 10.1128/jvi.69.1.585-588.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Umbricht C. B., Erdile L. F., Jabs E. W., Kelly T. J. Cloning, overexpression, and genomic mapping of the 14-kDa subunit of human replication protein A. J Biol Chem. 1993 Mar 25;268(9):6131–6138. [PubMed] [Google Scholar]
  34. Wold M. S., Kelly T. Purification and characterization of replication protein A, a cellular protein required for in vitro replication of simian virus 40 DNA. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2523–2527. doi: 10.1073/pnas.85.8.2523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wold M. S., Weinberg D. H., Virshup D. M., Li J. J., Kelly T. J. Identification of cellular proteins required for simian virus 40 DNA replication. J Biol Chem. 1989 Feb 15;264(5):2801–2809. [PubMed] [Google Scholar]
  36. 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]
  37. 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]
  38. 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]

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