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. 1990 Dec;64(12):5812–5822. doi: 10.1128/jvi.64.12.5812-5822.1990

Identification of critical elements within the JC virus DNA replication origin.

K J Lynch 1, R J Frisque 1
PMCID: PMC248737  PMID: 2173768

Abstract

The T antigen of JC virus (JCV) does not interact productively with the simian virus 40 (SV40) origin of replication. In contrast, the SV40 T antigen does drive replication from the JCV origin as well as from its own. The basis for this restricted interaction was investigated by analyzing the structure of the JCV replication origin. The replication activities of JCV-SV40 hybrid origin plasmids were tested in cells constitutively producing either the JCV or SV40 T antigen. Results indicated that a region of the JCV origin critical for interaction with the JCV T antigen was positioned to the late side of the central palindrome of the putative core origin. A mutational analysis of this region indicated that the sequence of the A + T-rich tract was primarily responsible for determining the efficiency with which JCV can initiate replication from its origin. The tandemly repeated pentameric sequence AGGGA located proximal to the A + T-rich tract in the JCV enhancer element was found to stimulate JCV, but not SV40, T antigen-mediated replication. The effect on replication of other elements within the JCV enhancer was also dependent on the T antigen employed for initiation. A plasmid containing the replication origin of prototype BK virus was unable to replicate in cells containing JCV T antigen, again indicating the inflexibility of the JCV T antigen in interacting with heterologous origins.

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Selected References

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

  1. Amemiya K., Traub R., Durham L., Major E. O. Interaction of a nuclear factor-1-like protein with the regulatory region of the human polyomavirus JC virus. J Biol Chem. 1989 Apr 25;264(12):7025–7032. [PubMed] [Google Scholar]
  2. Amirhaeri S., Wohlrab F., Major E. O., Wells R. D. Unusual DNA structure in the regulatory region of the human papovavirus JC virus. J Virol. 1988 Mar;62(3):922–931. doi: 10.1128/jvi.62.3.922-931.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baur C. P., Knippers R. Protein-induced bending of the simian virus 40 origin of replication. J Mol Biol. 1988 Oct 20;203(4):1009–1019. doi: 10.1016/0022-2836(88)90125-8. [DOI] [PubMed] [Google Scholar]
  4. Bergsma D. J., Olive D. M., Hartzell S. W., Subramanian K. N. Territorial limits and functional anatomy of the simian virus 40 replication origin. Proc Natl Acad Sci U S A. 1982 Jan;79(2):381–385. doi: 10.1073/pnas.79.2.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Borowiec J. A., Dean F. B., Bullock P. A., Hurwitz J. Binding and unwinding--how T antigen engages the SV40 origin of DNA replication. Cell. 1990 Jan 26;60(2):181–184. doi: 10.1016/0092-8674(90)90730-3. [DOI] [PubMed] [Google Scholar]
  6. Chandrasekharappa S. C., Subramanian K. N. Effects of position and orientation of the 72-base-pair-repeat transcriptional enhancer on replication from the simian virus 40 core origin. J Virol. 1987 Oct;61(10):2973–2980. doi: 10.1128/jvi.61.10.2973-2980.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Chuke W. F., Walker D. L., Peitzman L. B., Frisque R. J. Construction and characterization of hybrid polyomavirus genomes. J Virol. 1986 Dec;60(3):960–971. doi: 10.1128/jvi.60.3.960-971.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DeLucia A. L., Deb S., Partin K., Tegtmeyer P. Functional interactions of the simian virus 40 core origin of replication with flanking regulatory sequences. J Virol. 1986 Jan;57(1):138–144. doi: 10.1128/jvi.57.1.138-144.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DeLucia A. L., Lewton B. A., Tjian R., Tegtmeyer P. Topography of simian virus 40 A protein-DNA complexes: arrangement of pentanucleotide interaction sites at the origin of replication. J Virol. 1983 Apr;46(1):143–150. doi: 10.1128/jvi.46.1.143-150.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dean F. B., Bullock P., Murakami Y., Wobbe C. R., Weissbach L., Hurwitz J. Simian virus 40 (SV40) DNA replication: SV40 large T antigen unwinds DNA containing the SV40 origin of replication. Proc Natl Acad Sci U S A. 1987 Jan;84(1):16–20. doi: 10.1073/pnas.84.1.16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Deb S., DeLucia A. L., Baur C. P., Koff A., Tegtmeyer P. Domain structure of the simian virus 40 core origin of replication. Mol Cell Biol. 1986 May;6(5):1663–1670. doi: 10.1128/mcb.6.5.1663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Deb S., DeLucia A. L., Koff A., Tsui S., Tegtmeyer P. The adenine-thymine domain of the simian virus 40 core origin directs DNA bending and coordinately regulates DNA replication. Mol Cell Biol. 1986 Dec;6(12):4578–4584. doi: 10.1128/mcb.6.12.4578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Deb S., Tsui S., Koff A., DeLucia A. L., Parsons R., Tegtmeyer P. The T-antigen-binding domain of the simian virus 40 core origin of replication. J Virol. 1987 Jul;61(7):2143–2149. doi: 10.1128/jvi.61.7.2143-2149.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Del Vecchio A. M., Steinman R. A., Ricciardi R. P. An element of the BK virus enhancer required for DNA replication. J Virol. 1989 Apr;63(4):1514–1524. doi: 10.1128/jvi.63.4.1514-1524.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Deyerle K. L., Sajjadi F. G., Subramani S. Analysis of origin of DNA replication of human papovavirus BK. J Virol. 1989 Jan;63(1):356–365. doi: 10.1128/jvi.63.1.356-365.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. DiMaio D., Nathans D. Cold-sensitive regulatory mutants of simian virus 40. J Mol Biol. 1980 Jun 15;140(1):129–142. doi: 10.1016/0022-2836(80)90359-9. [DOI] [PubMed] [Google Scholar]
  18. DiMaio D., Nathans D. Regulatory mutants of simian virus 40. Effect of mutations at a T antigen binding site on DNA replication and expression of viral genes. J Mol Biol. 1982 Apr 15;156(3):531–548. doi: 10.1016/0022-2836(82)90265-0. [DOI] [PubMed] [Google Scholar]
  19. Dodson M., Dean F. B., Bullock P., Echols H., Hurwitz J. Unwinding of duplex DNA from the SV40 origin of replication by T antigen. Science. 1987 Nov 13;238(4829):964–967. doi: 10.1126/science.2823389. [DOI] [PubMed] [Google Scholar]
  20. Feigenbaum L., Khalili K., Major E., Khoury G. Regulation of the host range of human papovavirus JCV. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3695–3698. doi: 10.1073/pnas.84.11.3695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Frisque R. J., Bream G. L., Cannella M. T. Human polyomavirus JC virus genome. J Virol. 1984 Aug;51(2):458–469. doi: 10.1128/jvi.51.2.458-469.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Fromm M., Berg P. Deletion mapping of DNA regions required for SV40 early region promoter function in vivo. J Mol Appl Genet. 1982;1(5):457–481. [PubMed] [Google Scholar]
  23. Gardner S. D., Field A. M., Coleman D. V., Hulme B. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet. 1971 Jun 19;1(7712):1253–1257. doi: 10.1016/s0140-6736(71)91776-4. [DOI] [PubMed] [Google Scholar]
  24. Gluzman Y., Frisque R. J., Sambrook J. Origin-defective mutants of SV40. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):293–300. doi: 10.1101/sqb.1980.044.01.033. [DOI] [PubMed] [Google Scholar]
  25. Gluzman Y. SV40-transformed simian cells support the replication of early SV40 mutants. Cell. 1981 Jan;23(1):175–182. doi: 10.1016/0092-8674(81)90282-8. [DOI] [PubMed] [Google Scholar]
  26. Guo Z. S., Gutierrez C., Heine U., Sogo J. M., Depamphilis M. L. Origin auxiliary sequences can facilitate initiation of simian virus 40 DNA replication in vitro as they do in vivo. Mol Cell Biol. 1989 Sep;9(9):3593–3602. doi: 10.1128/mcb.9.9.3593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hertz G. Z., Mertz J. E. Bidirectional promoter elements of simian virus 40 are required for efficient replication of the viral DNA. Mol Cell Biol. 1986 Oct;6(10):3513–3522. doi: 10.1128/mcb.6.10.3513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  29. Jones K. A., Myers R. M., Tjian R. Mutational analysis of simian virus 40 large T antigen DNA binding sites. EMBO J. 1984 Dec 20;3(13):3247–3255. doi: 10.1002/j.1460-2075.1984.tb02286.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kumar R., Yoon K. P., Subramanian K. N. Replication from a proximal simian virus 40 origin is severely inhibited by multiple reiterations of the 72-base-pair repeat enhancer sequence. Mol Cell Biol. 1988 Apr;8(4):1509–1517. doi: 10.1128/mcb.8.4.1509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lee-Chen G. J., Woodworth-Gutai M. Simian virus 40 DNA replication: functional organization of regulatory elements. Mol Cell Biol. 1986 Sep;6(9):3086–3093. doi: 10.1128/mcb.6.9.3086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Li J. J., Kelly T. J. Simian virus 40 DNA replication in vitro: specificity of initiation and evidence for bidirectional replication. Mol Cell Biol. 1985 Jun;5(6):1238–1246. doi: 10.1128/mcb.5.6.1238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Li J. J., Peden K. W., Dixon R. A., Kelly T. Functional organization of the simian virus 40 origin of DNA replication. Mol Cell Biol. 1986 Apr;6(4):1117–1128. doi: 10.1128/mcb.6.4.1117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Major E. O., Miller A. E., Mourrain P., Traub R. G., de Widt E., Sever J. Establishment of a line of human fetal glial cells that supports JC virus multiplication. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1257–1261. doi: 10.1073/pnas.82.4.1257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Malkas L. H., Baril E. F. Sequence recognition protein for the 17-base-pair A + T-rich tract in the replication origin of simian virus 40 DNA. Proc Natl Acad Sci U S A. 1989 Jan;86(1):70–74. doi: 10.1073/pnas.86.1.70. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Mandl C., Walker D. L., Frisque R. J. Derivation and characterization of POJ cells, transformed human fetal glial cells that retain their permissivity for JC virus. J Virol. 1987 Mar;61(3):755–763. doi: 10.1128/jvi.61.3.755-763.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Martin J. D., King D. M., Slauch J. M., Frisque R. J. Differences in regulatory sequences of naturally occurring JC virus variants. J Virol. 1985 Jan;53(1):306–311. doi: 10.1128/jvi.53.1.306-311.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Myers R. M., Tjian R. Construction and analysis of simian virus 40 origins defective in tumor antigen binding and DNA replication. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6491–6495. doi: 10.1073/pnas.77.11.6491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Nagata K., Guggenheimer R. A., Enomoto T., Lichy J. H., Hurwitz J. Adenovirus DNA replication in vitro: identification of a host factor that stimulates synthesis of the preterminal protein-dCMP complex. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6438–6442. doi: 10.1073/pnas.79.21.6438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Parsons R., Anderson M. E., Tegtmeyer P. Three domains in the simian virus 40 core origin orchestrate the binding, melting, and DNA helicase activities of T antigen. J Virol. 1990 Feb;64(2):509–518. doi: 10.1128/jvi.64.2.509-518.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rawlins D. R., Rosenfeld P. J., Wides R. J., Challberg M. D., Kelly T. J., Jr Structure and function of the adenovirus origin of replication. Cell. 1984 May;37(1):309–319. doi: 10.1016/0092-8674(84)90327-1. [DOI] [PubMed] [Google Scholar]
  42. Roberts J. M. Simian virus 40 (SV40) large tumor antigen causes stepwise changes in SV40 origin structure during initiation of DNA replication. Proc Natl Acad Sci U S A. 1989 Jun;86(11):3939–3943. doi: 10.1073/pnas.86.11.3939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Ryder K., Vakalopoulou E., Mertz R., Mastrangelo I., Hough P., Tegtmeyer P., Fanning E. Seventeen base pairs of region I encode a novel tripartite binding signal for SV40 T antigen. Cell. 1985 Sep;42(2):539–548. doi: 10.1016/0092-8674(85)90111-4. [DOI] [PubMed] [Google Scholar]
  44. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Seif I., Khoury G., Dhar R. The genome of human papovavirus BKV. Cell. 1979 Dec;18(4):963–977. doi: 10.1016/0092-8674(79)90209-5. [DOI] [PubMed] [Google Scholar]
  46. Shenk T. E., Carbon J., Berg P. Construction and analysis of viable deletion mutants of simian virus 40. J Virol. 1976 May;18(2):664–671. doi: 10.1128/jvi.18.2.664-671.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Shortle D., Nathans D. Regulatory mutants of simian virus 40: constructed mutants with base substitutions at the origin of DNA replication. J Mol Biol. 1979 Jul 15;131(4):801–817. doi: 10.1016/0022-2836(79)90202-x. [DOI] [PubMed] [Google Scholar]
  48. Sompayrac L. M., Danna K. J. Efficient infection of monkey cells with DNA of simian virus 40. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7575–7578. doi: 10.1073/pnas.78.12.7575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  50. Stahl H., Dröge P., Knippers R. DNA helicase activity of SV40 large tumor antigen. EMBO J. 1986 Aug;5(8):1939–1944. doi: 10.1002/j.1460-2075.1986.tb04447.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Stillman B., Gerard R. D., Guggenheimer R. A., Gluzman Y. T antigen and template requirements for SV40 DNA replication in vitro. EMBO J. 1985 Nov;4(11):2933–2939. doi: 10.1002/j.1460-2075.1985.tb04026.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Subramanian K. N., Shenk T. Definition of the boundaries of the origin of DNA replication in simian virus 40. Nucleic Acids Res. 1978 Oct;5(10):3635–3642. doi: 10.1093/nar/5.10.3635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Traut W., Fanning E. Sequence-specific interactions between a cellular DNA-binding protein and the simian virus 40 origin of DNA replication. Mol Cell Biol. 1988 Feb;8(2):903–911. doi: 10.1128/mcb.8.2.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Tsurimoto T., Stillman B. Purification of a cellular replication factor, RF-C, that is required for coordinated synthesis of leading and lagging strands during simian virus 40 DNA replication in vitro. Mol Cell Biol. 1989 Feb;9(2):609–619. doi: 10.1128/mcb.9.2.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Yamaguchi M., DePamphilis M. L. DNA binding site for a factor(s) required to initiate simian virus 40 DNA replication. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1646–1650. doi: 10.1073/pnas.83.6.1646. [DOI] [PMC free article] [PubMed] [Google Scholar]

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