Abstract
In a subclone of ID13 mouse fibroblasts latently infected with bovine papillomavirus type 1 (BPV-1) DNA, the viral genome occurred as a mixture of extrachromosomal circular monomers and oligomers. Multiple copies were also associated with the host cell genome, predominantly at a single site in a head-to-tail tandem array. We examined the replicative intermediates of extrachromosomal forms of BPV-1 DNA by using two-dimensional gel electrophoresis. The results obtained indicate that initiation of DNA replication occurred near the center of the EcoRI-BamHI 5.6-kilobase fragment. In some molecules, however, this fragment was replicated from one end to the other by means of a single fork initiated elsewhere. Termination also occurred within this fragment. The EcoRI-BamHI 2.3-kilobase fragment replicated as a DNA molecule containing a termination site for DNA replication and also by means of a single fork traversing the fragment from one end to the other. Thus, replication forks proceeded through these fragments in different manners, apparently depending on whether they were part of a monomer, a dimer, a trimer, or higher oligomers. These observations lead to the conclusion that initiation of DNA replication in BPV-1 DNA takes place at or close to plasmid maintenance sequence 1. From this point, replication proceeds bidirectionally and termination occurs approximately 180 degrees opposite the origin. The results obtained are consistent with one or more replication origins being quiescent in BPV-1 DNA oligomers.
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Selected References
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- Adolph S., Bartram C. R., Hameister H. Mapping of the oncogenes Myc, Sis, and int-1 to the distal part of mouse chromosome 15. Cytogenet Cell Genet. 1987;44(2-3):65–68. doi: 10.1159/000132345. [DOI] [PubMed] [Google Scholar]
- Bell L., Byers B. Separation of branched from linear DNA by two-dimensional gel electrophoresis. Anal Biochem. 1983 Apr 15;130(2):527–535. doi: 10.1016/0003-2697(83)90628-0. [DOI] [PubMed] [Google Scholar]
- Breitburd F., Favre M., Zoorob R., Fortin D., Orth G. Detection and characterization of viral genomes and search for tumoral antigens in two hamster cell lines derived from tumors induced by bovine papillomavirus type 1. Int J Cancer. 1981 May 15;27(5):693–702. doi: 10.1002/ijc.2910270517. [DOI] [PubMed] [Google Scholar]
- Brewer B. J., Fangman W. L. A replication fork barrier at the 3' end of yeast ribosomal RNA genes. Cell. 1988 Nov 18;55(4):637–643. doi: 10.1016/0092-8674(88)90222-x. [DOI] [PubMed] [Google Scholar]
- Brewer B. J., Fangman W. L. The localization of replication origins on ARS plasmids in S. cerevisiae. Cell. 1987 Nov 6;51(3):463–471. doi: 10.1016/0092-8674(87)90642-8. [DOI] [PubMed] [Google Scholar]
- Challberg M. D., Kelly T. J. Animal virus DNA replication. Annu Rev Biochem. 1989;58:671–717. doi: 10.1146/annurev.bi.58.070189.003323. [DOI] [PubMed] [Google Scholar]
- Chen E. Y., Howley P. M., Levinson A. D., Seeburg P. H. The primary structure and genetic organization of the bovine papillomavirus type 1 genome. Nature. 1982 Oct 7;299(5883):529–534. doi: 10.1038/299529a0. [DOI] [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]
- DiMaio D., Treisman R., Maniatis T. Bovine papillomavirus vector that propagates as a plasmid in both mouse and bacterial cells. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4030–4034. doi: 10.1073/pnas.79.13.4030. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dvoretzky I., Shober R., Chattopadhyay S. K., Lowy D. R. A quantitative in vitro focus assay for bovine papilloma virus. Virology. 1980 Jun;103(2):369–375. doi: 10.1016/0042-6822(80)90195-6. [DOI] [PubMed] [Google Scholar]
- Fangman W. L. Separation of very large DNA molecules by gel electrophoresis. Nucleic Acids Res. 1978 Mar;5(3):653–665. doi: 10.1093/nar/5.3.653. [DOI] [PMC free article] [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]
- Gilbert D. M., Cohen S. N. Bovine papilloma virus plasmids replicate randomly in mouse fibroblasts throughout S phase of the cell cycle. Cell. 1987 Jul 3;50(1):59–68. doi: 10.1016/0092-8674(87)90662-3. [DOI] [PubMed] [Google Scholar]
- 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]
- Howley P. M. The molecular biology of papillomavirus transformation. Warner-Lambert Parke-Davis Award Lecture. Am J Pathol. 1983 Dec;113(3):414–421. [PMC free article] [PubMed] [Google Scholar]
- Huberman J. A., Spotila L. D., Nawotka K. A., el-Assouli S. M., Davis L. R. The in vivo replication origin of the yeast 2 microns plasmid. Cell. 1987 Nov 6;51(3):473–481. doi: 10.1016/0092-8674(87)90643-x. [DOI] [PubMed] [Google Scholar]
- Lambert P. F., Baker C. C., Howley P. M. The genetics of bovine papillomavirus type 1. Annu Rev Genet. 1988;22:235–258. doi: 10.1146/annurev.ge.22.120188.001315. [DOI] [PubMed] [Google Scholar]
- Lancaster W. D. Apparent lack of integration of bovine papillomavirus DNA in virus-induced equine and bovine tumor cells and virus-transformed mouse cells. Virology. 1981 Jan 30;108(2):251–255. doi: 10.1016/0042-6822(81)90433-5. [DOI] [PubMed] [Google Scholar]
- Law M. F., Lowy D. R., Dvoretzky I., Howley P. M. Mouse cells transformed by bovine papillomavirus contain only extrachromosomal viral DNA sequences. Proc Natl Acad Sci U S A. 1981 May;78(5):2727–2731. doi: 10.1073/pnas.78.5.2727. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Linskens M. H., Huberman J. A. Organization of replication of ribosomal DNA in Saccharomyces cerevisiae. Mol Cell Biol. 1988 Nov;8(11):4927–4935. doi: 10.1128/mcb.8.11.4927. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lusky M., Botchan M. R. Characterization of the bovine papilloma virus plasmid maintenance sequences. Cell. 1984 Feb;36(2):391–401. doi: 10.1016/0092-8674(84)90232-0. [DOI] [PubMed] [Google Scholar]
- Martin M. A., Howley P. M., Byrne J. C., Garon C. F. Characterization of supercoiled oligomeric SV40 DNA molecules in productively infected cells. Virology. 1976 May;71(1):28–40. doi: 10.1016/0042-6822(76)90091-x. [DOI] [PubMed] [Google Scholar]
- McClintock B. The Production of Homozygous Deficient Tissues with Mutant Characteristics by Means of the Aberrant Mitotic Behavior of Ring-Shaped Chromosomes. Genetics. 1938 Jul;23(4):315–376. doi: 10.1093/genetics/23.4.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mecsas J., Sugden B. Replication of plasmids derived from bovine papilloma virus type 1 and Epstein-Barr virus in cells in culture. Annu Rev Cell Biol. 1987;3:87–108. doi: 10.1146/annurev.cb.03.110187.000511. [DOI] [PubMed] [Google Scholar]
- Nawotka K. A., Huberman J. A. Two-dimensional gel electrophoretic method for mapping DNA replicons. Mol Cell Biol. 1988 Apr;8(4):1408–1413. doi: 10.1128/mcb.8.4.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Petes T. D. Yeast ribosomal DNA genes are located on chromosome XII. Proc Natl Acad Sci U S A. 1979 Jan;76(1):410–414. doi: 10.1073/pnas.76.1.410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Philippsen P., Thomas M., Kramer R. A., Davis R. W. Unique arrangement of coding sequences for 5 S, 5.8 S, 18 S and 25 S ribosomal RNA in Saccharomyces cerevisiae as determined by R-loop and hybridization analysis. J Mol Biol. 1978 Aug 15;123(3):387–404. doi: 10.1016/0022-2836(78)90086-4. [DOI] [PubMed] [Google Scholar]
- Sarver N., Byrne J. C., Howley P. M. Transformation and replication in mouse cells of a bovine papillomavirus--pML2 plasmid vector that can be rescued in bacteria. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7147–7151. doi: 10.1073/pnas.79.23.7147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sarver N., Gruss P., Law M. F., Khoury G., Howley P. M. Bovine papilloma virus deoxyribonucleic acid: a novel eucaryotic cloning vector. Mol Cell Biol. 1981 Jun;1(6):486–496. doi: 10.1128/mcb.1.6.486. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sauer G., Amtmann E., Melber K., Knapp A., Müller K., Hummel K., Scherm A. DNA and RNA virus species are inhibited by xanthates, a class of antiviral compounds with unique properties. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3263–3267. doi: 10.1073/pnas.81.11.3263. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Skryabin K. G., Eldarov M. A., Larionov V. L., Bayev A. A., Klootwijk J., de Regt V. C., Veldman G. M., Planta R. J., Georgiev O. I., Hadjiolov A. A. Structure and function of the nontranscribed spacer regions of yeast rDNA. Nucleic Acids Res. 1984 Mar 26;12(6):2955–2968. doi: 10.1093/nar/12.6.2955. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith G. P. Evolution of repeated DNA sequences by unequal crossover. Science. 1976 Feb 13;191(4227):528–535. doi: 10.1126/science.1251186. [DOI] [PubMed] [Google Scholar]
- Tapper D. P., DePamphilis M. L. Preferred DNA sites are involved in the arrest and initiation of DNA synthesis during replication of SV40 DNA. Cell. 1980 Nov;22(1 Pt 1):97–108. doi: 10.1016/0092-8674(80)90158-0. [DOI] [PubMed] [Google Scholar]
- Umek R. M., Linskens M. H., Kowalski D., Huberman J. A. New beginnings in studies of eukaryotic DNA replication origins. Biochim Biophys Acta. 1989 Jan 23;1007(1):1–14. doi: 10.1016/0167-4781(89)90123-1. [DOI] [PubMed] [Google Scholar]
- Waldeck W., Rösl F., Zentgraf H. Origin of replication in episomal bovine papilloma virus type 1 DNA isolated from transformed cells. EMBO J. 1984 Sep;3(9):2173–2178. doi: 10.1002/j.1460-2075.1984.tb02109.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walmsley R. M., Johnston L. H., Williamson D. H., Oliver S. G. Replicon size of yeast ribosomal DNA. Mol Gen Genet. 1984;195(1-2):260–266. doi: 10.1007/BF00332757. [DOI] [PubMed] [Google Scholar]
- Wettstein F. O., Stevens J. G. Variable-sized free episomes of Shope papilloma virus DNA are present in all non-virus-producing neoplasms and integrated episomes are detected in some. Proc Natl Acad Sci U S A. 1982 Feb;79(3):790–794. doi: 10.1073/pnas.79.3.790. [DOI] [PMC free article] [PubMed] [Google Scholar]