Skip to main content
NCBI home page
The EMBO Journal logoLink to The EMBO Journal
. 1987 Jul;6(7):2011–2018. doi: 10.1002/j.1460-2075.1987.tb02465.x

The origin of bidirectional DNA replication in polyoma virus.

E A Hendrickson 1, C E Fritze 1, W R Folk 1, M L DePamphilis 1
PMCID: PMC553590  PMID: 2820716

Abstract

The nucleotide locations of RNA-p-DNA covalent linkages in polyoma virus (PyV) replicating DNA were mapped in the region containing the genetically required origin of DNA replication (ori). These linkages mark the initiation sites for RNA-primed DNA synthesis. A clear transition was identified between the presence of these linkages (discontinuous DNA synthesis) and their absence (continuous DNA synthesis) on each strand of ori. This demonstrated that PyV DNA replication, like simian virus 40 (SV40), is semi-discontinuous, and thus revealed the location of the origin of bidirectional DNA replication (OBR). The transition site on the template encoding PyV late mRNA occurred at the junction of ori-core and T-antigen binding site A. This was essentially the same site as previously observed in SV40 (Hay and DePamphilis, 1982). However, in contrast to SV40, the transition site on the template encoding PyV early mRNA was displaced towards the late gene side of ori. This resulted in a 16 nucleotide gap within ori in which no RNA-p-DNA linkages were observed on either strand. A model for the initiation of PyV DNA replication is presented.

Full text

PDF
2011

Images in this article

2013Fig. 2.
on p.2013
2014Fig. 3.
on p.2014
2015Fig. 4.
on p.2015

Selected References

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

  1. Anderson S., Kaufman G., DePamphilis M. L. RNA primers in SV40 DNA replication: identification of transient RNA-DNA covalent linkages in replicating DNA. Biochemistry. 1977 Nov 15;16(23):4990–4998. doi: 10.1021/bi00642a009. [DOI] [PubMed] [Google Scholar]
  2. Ariga H., Sugano S. Initiation of simian virus 40 DNA replication in vitro. J Virol. 1983 Nov;48(2):481–491. doi: 10.1128/jvi.48.2.481-491.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Buckler-White A. J., Krauss M. R., Pigiet V., Benbow R. M. Asynchronous bidirectional replication of polyoma virus DNA. J Virol. 1982 Sep;43(3):885–895. doi: 10.1128/jvi.43.3.885-895.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Böhnlein E., Gruss P. Interaction of distinct nuclear proteins with sequences controlling the expression of polyomavirus early genes. Mol Cell Biol. 1986 May;6(5):1401–1411. doi: 10.1128/mcb.6.5.1401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clayton D. A. Replication of animal mitochondrial DNA. Cell. 1982 Apr;28(4):693–705. doi: 10.1016/0092-8674(82)90049-6. [DOI] [PubMed] [Google Scholar]
  7. Cowie A., Kamen R. Guanine nucleotide contacts within viral DNA sequences bound by polyomavirus large T antigen. J Virol. 1986 Feb;57(2):505–514. doi: 10.1128/jvi.57.2.505-514.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. 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]
  11. Decker R. S., Yamaguchi M., Possenti R., DePamphilis M. L. Initiation of simian virus 40 DNA replication in vitro: aphidicolin causes accumulation of early-replicating intermediates and allows determination of the initial direction of DNA synthesis. Mol Cell Biol. 1986 Nov;6(11):3815–3825. doi: 10.1128/mcb.6.11.3815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Deninger P. L., Esty A., LaPorte P., Hsu H., Friedmann T. The nucleotide sequence and restriction enzyme sites of the polyoma genome. Nucleic Acids Res. 1980 Feb 25;8(4):855–860. [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Dilworth S. M., Cowie A., Kamen R. I., Griffin B. E. DNA binding activity of polyoma virus large tumor antigen. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1941–1945. doi: 10.1073/pnas.81.7.1941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Eliasson R., Reichard P. Replication of polyoma DNA in isolated nuclei. VII. Initiator RNA synthesis during nucleotide depletion. J Mol Biol. 1979 Apr 15;129(3):393–409. doi: 10.1016/0022-2836(79)90503-5. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Fujimura F. K. Nuclear activity from F9 embryonal carcinoma cells binding specifically to the enhancers of wild-type polyoma virus and PyEC mutant DNAs. Nucleic Acids Res. 1986 Apr 11;14(7):2845–2861. doi: 10.1093/nar/14.7.2845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hay R. T., DePamphilis M. L. Initiation of SV40 DNA replication in vivo: location and structure of 5' ends of DNA synthesized in the ori region. Cell. 1982 Apr;28(4):767–779. doi: 10.1016/0092-8674(82)90056-3. [DOI] [PubMed] [Google Scholar]
  19. Hay R. T., Hendrickson E. A., DePamphilis M. L. Sequence specificity for the initiation of RNA-primed simian virus 40 DNA synthesis in vivo. J Mol Biol. 1984 May 15;175(2):131–157. doi: 10.1016/0022-2836(84)90471-6. [DOI] [PubMed] [Google Scholar]
  20. Herbomel P., Bourachot B., Yaniv M. Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma. Cell. 1984 Dec;39(3 Pt 2):653–662. doi: 10.1016/0092-8674(84)90472-0. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Kaufmann G., Anderson S., DePamphilis M. L. RNA primers in Simian virus 40 DNA replication. II. Distribution of 5' terminal oligoribonucleotides in nascent DNA. J Mol Biol. 1977 Nov 5;116(3):549–567. doi: 10.1016/0022-2836(77)90083-3. [DOI] [PubMed] [Google Scholar]
  23. Kaufmann G., Bar-Shavit R., DePamphilis M. L. Okazaki pieces grow opposite to the replication fork direction during simian virus 40 DNA replication. Nucleic Acids Res. 1978 Jul;5(7):2535–2545. doi: 10.1093/nar/5.7.2535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kohara Y., Tohdoh N., Jiang X. W., Okazaki T. The distribution and properties of RNA primed initiation sites of DNA synthesis at the replication origin of Escherichia coli chromosome. Nucleic Acids Res. 1985 Oct 11;13(19):6847–6866. doi: 10.1093/nar/13.19.6847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Li J. J., Kelly T. J. Simian virus 40 DNA replication in vitro. Proc Natl Acad Sci U S A. 1984 Nov;81(22):6973–6977. doi: 10.1073/pnas.81.22.6973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Margolskee R. F., Nathans D. Simian virus 40 mutant T antigens with relaxed specificity for the nucleotide sequence at the viral DNA origin of replication. J Virol. 1984 Feb;49(2):386–393. doi: 10.1128/jvi.49.2.386-393.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  30. Mueller C. R., Mes-Masson A. M., Bouvier M., Hassell J. A. Location of sequences in polyomavirus DNA that are required for early gene expression in vivo and in vitro. Mol Cell Biol. 1984 Dec;4(12):2594–2609. doi: 10.1128/mcb.4.12.2594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Murakami Y., Eki T., Yamada M., Prives C., Hurwitz J. Species-specific in vitro synthesis of DNA containing the polyoma virus origin of replication. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6347–6351. doi: 10.1073/pnas.83.17.6347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Murakami Y., Wobbe C. R., Weissbach L., Dean F. B., Hurwitz J. Role of DNA polymerase alpha and DNA primase in simian virus 40 DNA replication in vitro. Proc Natl Acad Sci U S A. 1986 May;83(9):2869–2873. doi: 10.1073/pnas.83.9.2869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Okazaki R., Hirose S., Okazaki T., Ogawa T., Kurosawa Y. Assay of RNA-linked nascent DNA pieces with polynucleotide kinase. Biochem Biophys Res Commun. 1975 Feb 17;62(4):1018–1024. doi: 10.1016/0006-291x(75)90424-6. [DOI] [PubMed] [Google Scholar]
  34. Ostapchuk P., Diffley J. F., Bruder J. T., Stillman B., Levine A. J., Hearing P. Interaction of a nuclear factor with the polyomavirus enhancer region. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8550–8554. doi: 10.1073/pnas.83.22.8550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Perlman D., Huberman J. A. Asymmetric Okazaki piece synthesis during replication of simian virus 40 DNA in vivo. Cell. 1977 Dec;12(4):1029–1043. doi: 10.1016/0092-8674(77)90167-2. [DOI] [PubMed] [Google Scholar]
  36. Piette J., Yaniv M. Molecular analysis of the interaction between an enhancer binding factor and its DNA target. Nucleic Acids Res. 1986 Dec 22;14(24):9595–9611. doi: 10.1093/nar/14.24.9595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Reichard P., Eliasson R., Söderman G. Initiator RNA in discontinuous polyoma DNA synthesis. Proc Natl Acad Sci U S A. 1974 Dec;71(12):4901–4905. doi: 10.1073/pnas.71.12.4901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rothwell V. M., Folk W. R. Comparison of the DNA sequence of the Crawford small-plaque variant of polyomavirus with those of polyomaviruses A2 and strain 3. J Virol. 1983 Nov;48(2):472–480. doi: 10.1128/jvi.48.2.472-480.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Shortle D. R., Margolskee R. F., Nathans D. Mutational analysis of the simian virus 40 replicon: pseudorevertants of mutants with a defective replication origin. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6128–6131. doi: 10.1073/pnas.76.12.6128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Smale S. T., Tjian R. T-antigen-DNA polymerase alpha complex implicated in simian virus 40 DNA replication. Mol Cell Biol. 1986 Nov;6(11):4077–4087. doi: 10.1128/mcb.6.11.4077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. Tegtmeyer P., Lewton B. A., DeLucia A. L., Wilson V. G., Ryder K. Topography of simian virus 40 A protein-DNA complexes: arrangement of protein bound to the origin of replication. J Virol. 1983 Apr;46(1):151–161. doi: 10.1128/jvi.46.1.151-161.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Tjian R. The binding site on SV40 DNA for a T antigen-related protein. Cell. 1978 Jan;13(1):165–179. doi: 10.1016/0092-8674(78)90147-2. [DOI] [PubMed] [Google Scholar]
  44. Triezenberg S. J., Folk W. R. Essential nucleotides in the polyomavirus origin region. J Virol. 1984 Aug;51(2):437–444. doi: 10.1128/jvi.51.2.437-444.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tsurimoto T., Matsubara K. Multiple initiation sites of DNA replication flanking the origin region of lambda dv genome. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7402–7406. doi: 10.1073/pnas.81.23.7402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Veldman G. M., Lupton S., Kamen R. Polyomavirus enhancer contains multiple redundant sequence elements that activate both DNA replication and gene expression. Mol Cell Biol. 1985 Apr;5(4):649–658. doi: 10.1128/mcb.5.4.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. 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]
  48. Yamaguchi M., Hendrickson E. A., DePamphilis M. L. DNA primase-DNA polymerase alpha from simian cells: sequence specificity of initiation sites on simian virus 40 DNA. Mol Cell Biol. 1985 May;5(5):1170–1183. doi: 10.1128/mcb.5.5.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES