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. 1992 Jan;66(1):420–431. doi: 10.1128/jvi.66.1.420-431.1992

In vivo resolution of circular plasmids containing concatemer junction fragments from minute virus of mice DNA and their subsequent replication as linear molecules.

S F Cotmore 1, P Tattersall 1
PMCID: PMC238302  PMID: 1530771

Abstract

During replication of their linear, single-stranded DNA genomes, parvoviruses generate a series of concatemeric duplex intermediates. We have cloned, into Escherichia coli plasmids, junction fragments from these palindromic concatemers of minute virus of mice DNA spanning both the right end-to-right end (viral 5' to 5') and left end-to-left end (viral 3' to 3') fusions. When mouse cells were transfected with these circular plasmids and superinfected with minute virus of mice, the viral junctions were resolved and the plasmids replicated as linear chromosomes with vector DNA in their centers and viral DNA at their termini. Resolution did not occur when the concatemer joint was replaced by a different palindromic sequence or when the transfected cells were not superinfected, indicating the presence of latent origins of replication which could only be activated by a viral trans-acting factor(s). Moreover, the products of resolution and replication from the two termini were characteristically different. Analysis of individual terminal fragments showed that viral 5' (right-end) sequences were resolved predominantly into "extended" structures with covalently associated copies of the virally encoded NS-1 polypeptide, while bridges derived from the 3' (left) end resolved into both NS-1-associated extended termini and lower-molecular-weight "turn-around" forms in which the two DNA strands were covalently continuous. This pattern of resolution exactly coincides with that seen at the two termini of replicative-form intermediates in normal virus infections. These results demonstrate that the bridge structures are authentic substrates for resolution and indicate that the frequency with which extended versus turn-around forms of each terminus are generated is an intrinsic property of the telomere.

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Selected References

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  1. Astell C. R., Chow M. B., Ward D. C. Sequence analysis of the termini of virion and replicative forms of minute virus of mice DNA suggests a modified rolling hairpin model for autonomous parvovirus DNA replication. J Virol. 1985 Apr;54(1):171–177. doi: 10.1128/jvi.54.1.171-177.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Astell C. R., Thomson M., Chow M. B., Ward D. C. Structure and replication of minute virus of mice DNA. Cold Spring Harb Symp Quant Biol. 1983;47(Pt 2):751–762. doi: 10.1101/sqb.1983.047.01.086. [DOI] [PubMed] [Google Scholar]
  3. Astell C. R., Thomson M., Merchlinsky M., Ward D. C. The complete DNA sequence of minute virus of mice, an autonomous parvovirus. Nucleic Acids Res. 1983 Feb 25;11(4):999–1018. doi: 10.1093/nar/11.4.999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berns K. I., Hauswirth W. W. Adeno-associated viruses. Adv Virus Res. 1979;25:407–449. doi: 10.1016/s0065-3527(08)60574-6. [DOI] [PubMed] [Google Scholar]
  5. Berns K. I. Parvovirus replication. Microbiol Rev. 1990 Sep;54(3):316–329. doi: 10.1128/mr.54.3.316-329.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boissy R., Astell C. R. An Escherichia coli recBCsbcBrecF host permits the deletion-resistant propagation of plasmid clones containing the 5'-terminal palindrome of minute virus of mice. Gene. 1985;35(1-2):179–185. doi: 10.1016/0378-1119(85)90170-2. [DOI] [PubMed] [Google Scholar]
  7. Brandenburger A., Legendre D., Avalosse B., Rommelaere J. NS-1 and NS-2 proteins may act synergistically in the cytopathogenicity of parvovirus MVMp. Virology. 1990 Feb;174(2):576–584. doi: 10.1016/0042-6822(90)90110-d. [DOI] [PubMed] [Google Scholar]
  8. Chen K. C., Shull B. C., Lederman M., Stout E. R., Bates R. C. Analysis of the termini of the DNA of bovine parvovirus: demonstration of sequence inversion at the left terminus and its implication for the replication model. J Virol. 1988 Oct;62(10):3807–3813. doi: 10.1128/jvi.62.10.3807-3813.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chen K. C., Tyson J. J., Lederman M., Stout E. R., Bates R. C. A kinetic hairpin transfer model for parvoviral DNA replication. J Mol Biol. 1989 Jul 20;208(2):283–296. doi: 10.1016/0022-2836(89)90389-6. [DOI] [PubMed] [Google Scholar]
  10. Cotmore S. F., Gunther M., Tattersall P. Evidence for a ligation step in the DNA replication of the autonomous parvovirus minute virus of mice. J Virol. 1989 Feb;63(2):1002–1006. doi: 10.1128/jvi.63.2.1002-1006.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cotmore S. F., Tattersall P. A genome-linked copy of the NS-1 polypeptide is located on the outside of infectious parvovirus particles. J Virol. 1989 Sep;63(9):3902–3911. doi: 10.1128/jvi.63.9.3902-3911.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cotmore S. F., Tattersall P. Organization of nonstructural genes of the autonomous parvovirus minute virus of mice. J Virol. 1986 Jun;58(3):724–732. doi: 10.1128/jvi.58.3.724-732.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cotmore S. F., Tattersall P. The NS-1 polypeptide of minute virus of mice is covalently attached to the 5' termini of duplex replicative-form DNA and progeny single strands. J Virol. 1988 Mar;62(3):851–860. doi: 10.1128/jvi.62.3.851-860.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Cotmore S. F., Tattersall P. The autonomously replicating parvoviruses of vertebrates. Adv Virus Res. 1987;33:91–174. doi: 10.1016/s0065-3527(08)60317-6. [DOI] [PubMed] [Google Scholar]
  15. DeLange A. M., Reddy M., Scraba D., Upton C., McFadden G. Replication and resolution of cloned poxvirus telomeres in vivo generates linear minichromosomes with intact viral hairpin termini. J Virol. 1986 Aug;59(2):249–259. doi: 10.1128/jvi.59.2.249-259.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dickie P., Morgan A. R., McFadden G. Cruciform extrusion in plasmids bearing the replicative intermediate configuration of a poxvirus telomere. J Mol Biol. 1987 Aug 5;196(3):541–558. doi: 10.1016/0022-2836(87)90031-3. [DOI] [PubMed] [Google Scholar]
  17. Diffoot N., Shull B. C., Chen K. C., Stout E. R., Lederman M., Bates R. C. Identical ends are not required for the equal encapsidation of plus- and minus-strand parvovirus LuIII DNA. J Virol. 1989 Jul;63(7):3180–3184. doi: 10.1128/jvi.63.7.3180-3184.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Eisenberg S., Griffith J., Kornberg A. phiX174 cistron A protein is a multifunctional enzyme in DNA replication. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3198–3202. doi: 10.1073/pnas.74.8.3198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Eisenberg S., Kornberg A. Purification and characterization of phiX174 gene A protein. A multifunctional enzyme of duplex DNA replication. J Biol Chem. 1979 Jun 25;254(12):5328–5332. [PubMed] [Google Scholar]
  20. Faust E. A., Ward D. C. Incomplete genomes of the parvovirus minute virus of mice: selective conservation of genome termini, including the origin for DNA replication. J Virol. 1979 Oct;32(1):276–292. doi: 10.1128/jvi.32.1.276-292.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hermonat P. L., Labow M. A., Wright R., Berns K. I., Muzyczka N. Genetics of adeno-associated virus: isolation and preliminary characterization of adeno-associated virus type 2 mutants. J Virol. 1984 Aug;51(2):329–339. doi: 10.1128/jvi.51.2.329-339.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Im D. S., Muzyczka N. The AAV origin binding protein Rep68 is an ATP-dependent site-specific endonuclease with DNA helicase activity. Cell. 1990 May 4;61(3):447–457. doi: 10.1016/0092-8674(90)90526-k. [DOI] [PubMed] [Google Scholar]
  24. Labow M. A., Graf L. H., Jr, Berns K. I. Adeno-associated virus gene expression inhibits cellular transformation by heterologous genes. Mol Cell Biol. 1987 Apr;7(4):1320–1325. doi: 10.1128/mcb.7.4.1320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Labow M. A., Hermonat P. L., Berns K. I. Positive and negative autoregulation of the adeno-associated virus type 2 genome. J Virol. 1986 Oct;60(1):251–258. doi: 10.1128/jvi.60.1.251-258.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Merchlinsky M., Garon C. F., Moss B. Molecular cloning and sequence of the concatemer junction from vaccinia virus replicative DNA. Viral nuclease cleavage sites in cruciform structures. J Mol Biol. 1988 Feb 5;199(3):399–413. doi: 10.1016/0022-2836(88)90613-4. [DOI] [PubMed] [Google Scholar]
  27. Merchlinsky M., Moss B. Nucleotide sequence required for resolution of the concatemer junction of vaccinia virus DNA. J Virol. 1989 Oct;63(10):4354–4361. doi: 10.1128/jvi.63.10.4354-4361.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Merchlinsky M., Moss B. Resolution of linear minichromosomes with hairpin ends from circular plasmids containing vaccinia virus concatemer junctions. Cell. 1986 Jun 20;45(6):879–884. doi: 10.1016/0092-8674(86)90562-3. [DOI] [PubMed] [Google Scholar]
  29. Merchlinsky M., Moss B. Resolution of vaccinia virus DNA concatemer junctions requires late-gene expression. J Virol. 1989 Apr;63(4):1595–1603. doi: 10.1128/jvi.63.4.1595-1603.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rhode S. L., 3rd Both excision and replication of cloned autonomous parvovirus DNA require the NS1 (rep) protein. J Virol. 1989 Oct;63(10):4249–4256. doi: 10.1128/jvi.63.10.4249-4256.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rhode S. L., 3rd trans-Activation of parvovirus P38 promoter by the 76K noncapsid protein. J Virol. 1985 Sep;55(3):886–889. doi: 10.1128/jvi.55.3.886-889.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Samulski R. J., Chang L. S., Shenk T. Helper-free stocks of recombinant adeno-associated viruses: normal integration does not require viral gene expression. J Virol. 1989 Sep;63(9):3822–3828. doi: 10.1128/jvi.63.9.3822-3828.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Shade R. O., Blundell M. C., Cotmore S. F., Tattersall P., Astell C. R. Nucleotide sequence and genome organization of human parvovirus B19 isolated from the serum of a child during aplastic crisis. J Virol. 1986 Jun;58(3):921–936. doi: 10.1128/jvi.58.3.921-936.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Siegl G., Bates R. C., Berns K. I., Carter B. J., Kelly D. C., Kurstak E., Tattersall P. Characteristics and taxonomy of Parvoviridae. Intervirology. 1985;23(2):61–73. doi: 10.1159/000149587. [DOI] [PubMed] [Google Scholar]
  35. Snyder R. O., Im D. S., Muzyczka N. Evidence for covalent attachment of the adeno-associated virus (AAV) rep protein to the ends of the AAV genome. J Virol. 1990 Dec;64(12):6204–6213. doi: 10.1128/jvi.64.12.6204-6213.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Snyder R. O., Samulski R. J., Muzyczka N. In vitro resolution of covalently joined AAV chromosome ends. Cell. 1990 Jan 12;60(1):105–113. doi: 10.1016/0092-8674(90)90720-y. [DOI] [PubMed] [Google Scholar]
  37. Straus S. E., Sebring E. D., Rose J. A. Concatemers of alternating plus and minus strands are intermediates in adenovirus-associated virus DNA synthesis. Proc Natl Acad Sci U S A. 1976 Mar;73(3):742–746. doi: 10.1073/pnas.73.3.742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tattersall P., Bratton J. Reciprocal productive and restrictive virus-cell interactions of immunosuppressive and prototype strains of minute virus of mice. J Virol. 1983 Jun;46(3):944–955. doi: 10.1128/jvi.46.3.944-955.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Tattersall P., Ward D. C. Rolling hairpin model for replication of parvovirus and linear chromosomal DNA. Nature. 1976 Sep 9;263(5573):106–109. doi: 10.1038/263106a0. [DOI] [PubMed] [Google Scholar]
  40. Tratschin J. D., Miller I. L., Carter B. J. Genetic analysis of adeno-associated virus: properties of deletion mutants constructed in vitro and evidence for an adeno-associated virus replication function. J Virol. 1984 Sep;51(3):611–619. doi: 10.1128/jvi.51.3.611-619.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tratschin J. D., Tal J., Carter B. J. Negative and positive regulation in trans of gene expression from adeno-associated virus vectors in mammalian cells by a viral rep gene product. Mol Cell Biol. 1986 Aug;6(8):2884–2894. doi: 10.1128/mcb.6.8.2884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Tyson J. J., Chen K. C., Lederman M., Bates R. C. Analysis of the kinetic hairpin transfer model for parvoviral DNA replication. J Theor Biol. 1990 May 22;144(2):155–169. doi: 10.1016/s0022-5193(05)80316-9. [DOI] [PubMed] [Google Scholar]
  43. Wigler M., Pellicer A., Silverstein S., Axel R., Urlaub G., Chasin L. DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373–1376. doi: 10.1073/pnas.76.3.1373. [DOI] [PMC free article] [PubMed] [Google Scholar]

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