Overview
We have begun an analysis of DNA sequences that function in the control of DNA replication in eukaryotic cells. Bovine papillomavirus (BPV) replicates as an extrachromosomal nuclear plasmid, duplicating each viral genome in synchrony with the host-cell DNA once and only once per cell division. Simian virus 40 (SV40) replication, however, is unresponsive to cellular controls, so the viral DNA replicates exponentially within the host-cell nucleus. To approach our study of the mechanisms of replication control, we designed a model system consisting of SV40 and BPV DNA sequences linked to create a hybrid replicon. We have obtained evidence that a main feature of copy-number regulation in the composite SV40-BPV plasmid is the imposition of dominant negative control encoded by BPV, which overrides the runaway replication induced by the positive factor, SV40 large tumor (large-T) antigen. Using a transient replication assay, we have previously been able to define the elements in the BPV genome that are sufficient to establish controlled replication in composite SV40-BPV plasmids (Roberts and Weintraub, 1986). These elements consist of two cis-acting sequences that are closely linked to BPV replication origins and a third element that acts in trans. The latter is encoded within the 5′ part of the E1 open reading frame (ORF) of the BPV genome and is physically and functionally separable from the positive replication factor encoded within the 3′ part of the same ORF. The controlled replication of SV40-BPV composite plasmids has enabled us to create permanent COS cell lines that stably maintain these plasmids as episomes.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Alt, F. W., Kellems, R. E., Bertino, J. R., and Schimke, R. T., 1978, Selective multiplication of dihydrofolate reductase genes in methotrexate resistant variants of cultured murine cells, J. Biol. Chem. 252:1357–1370.
Ariga, H., and Sugano, S., 1983, Initiation of simian virus 40 DNA replication in vitro, J. Virol. 48:481–491.
Berg, L., Singh, K., and Botchan, M., 1986, Complementation of a BPV low copy number mutant: Evidence for a temporal requirement of the complementing gene, Mol. Cell. Biol. (in press).
Blumenthal, A. B., Kriegstein, H. J., and Hogness, D. S., 1973, The units of DNA replication in Drosophila melanogaster chromosomes, Cold Spring Harbor Symp. Quant. Biol. 38:205–223.
Botchan, M., Topp, W., and Sambrook, J., 1978, Studies on simian virus 40 excision from cellular chromosomes, Cold Spring Harbor Symp. Quant. Biol. 43:708–720.
Brown, D. D., and Dawid, I. B., 1986, Specific gene amplification in oocytes, Science 160:272–280.
Chen, E.Y., Howley, P.M., Levinson, A. D., and Seeburg, P., 1982, The primary structure and genetic organization of the bovine papilloma-virus type I genome, Nature (London) 299:529–534.
Colbere-Garapin, F., Horodniceanu, F., Kourilsky, P., and Garapin, A. C., 1981, A new dominant hybrid selective marker for higher eukaryotic cells, J. Mol. Biol. 150:1–14.
DeLucia, A. L., Deb, S., Partin, K., and Tegtmeyer, P., 1986, Functional interactions of the simian virus 40 core origin of replication with flanking regulatory sequences, J. Virol. 57:138–144.
DiMaio, D., Treisman, R., and Maniatis, T., 1982, Bovine papilloma virus vector that propagates as a plasmid in both mouse and bacterial cells, Proc. Natl. Acad. Sci. U.S.A. 79:4030–4034.
DuBridge, R. B., Lusky, M., Botchan, M. R., and Calos, M. P., 1985, Amplification of a bovine papillomavirus-simian virus 40 chimera, J. Virol. 56:625–627.
Glover, D. M., Zaha, A., Stocker, A. J., Santelli, R. V., Pueyo, M. T., deToledo, S. M., and Lara, F. J. S., 1982, Gene amplification in Rhynchosciara salivary gland chromosomes, Proc. Natl. Acad. Sci. U.S.A. 79:2947–2951.
Gluzman, Y., 1981, SV40-transformed simian cells support the replication of early SV40 mutants, Cell 23:175–182.
Hand, R., 1978, Eukaryotic DNA: Organization of the genome for replication, Cell 15:317–325.
Harland, R. M., and Laskey, R. A., 1980, Regulation replication of DNA microinjected into eggs of Xenopus laevis, Cell 21:761–771.
Heilman, C. A., Engel, L., Lowy, D. R., and Howley, P. M., 1982, Virus specific transcription in bovine papillomavirus transformed mouse cells, Virology 119:22–34.
Jimenez, A., and Davies, Y., 1980, Expression of a transposable antibiotic resistance element in Saccharomyces, Nature (London) 287:869–871.
Keshet, I., Lieman-Hurwitz, J., and Cedar, H., 1986, DNA methylation affects the formation of active chromatin, Cell 44:535–543.
Klar, A. J. S., Strathern, J. N., and Hicks, J. B., 1985, Developmental pathways in yeast, in: Microbial Development (R. Losick and L. Shapiro, eds.), Cold Spring Harbor Laboratories, Cold Spring Harbor, New York, pp. 151–195.
Lavi, S., 1981, Carcinogen mediated amplification of viral DNA sequences in SV40 transformed Chinese hamster embryo cells, Proc. Natl. Acad. Sci. U.S.A. 78:6144–6148.
Lancaster, W. D., 1981, Apparent lack of integration of bovine papilloma virus DNA in virus-induced equine and bovine tumor cells and virus transformed mouse cells, Virology 108:251–255.
Law, M.-F., Lowy, D. R., Dvoretzky, J., and Howley, P. M., 1981, Mouse cells transformed by bovine papillomavirus contain only extra-chromosomal viral DNA sequences, Proc. Natl. Acad. Sci. U.S.A. 78:2727–2731.
Li, J. J., and Kelly, T. J., 1984, Simian virus 40 DNA replication in vitro, Proc. Natl. Acad. Sci. U.S.A. 81:6973–6977.
Lowy, D. R., Dvoretzky, I., Shober, R., Law, M.-F., Engel, L., and Howley, P. M., 1980, In vitro tumorigenic transformation by a defined sub-genomic fragment of bovine papilloma virus DNA, Nature (London) 287:72–74.
Lusky, M., and Botchan, M., 1981, Inhibition of SV40 replication in simian cells by specific pBR322 DNA sequences, Nature (London) 293:79–81.
Lusky, M., and Botchan, M., 1984, Characterization of the bovine papillomavirus plasmid maintenance sequences, Cell 36:391–401.
Lusky, M., and Botchan, M., 1985, Genetic analysis of bovine papillomavirus type 1 trans-acting replication factors, J. Virol. 53:955–965.
Lusky, M., and Botchan, M., 1986, Transient replication of BPV-1 plasmids: Cis and trans requirements, Proc. Natl. Acad. Sci. U.S.A. (in press).
Lusky, M., Berg, L., Weiher, H., and Botchan, M., 1983, Bovine papilloma virus contains an activator of gene expression at the distal end of the early transcription unit, Mol. Cell. Biol. 3:1108–1122.
Meyers, R., and Tjian, R., 1980, Construction and analysis of simian virus 40 origins defective in tumor antigen binding and DNA replication, Proc. Natl. Acad. Sci. U.S.A. 77:6491–6495.
Miller, A. M., and Nasmyth, K. A., 1984, Role of DNA replication in the repression of silent mating type loci in yeast, Nature (London) 312:247–251.
Muriani, B., and Schimke, R., 1984, Gene amplification in a simple cell cycle in Chinese hamster ovary cells, J. Biol. Chem. 258:1901–1910.
Nasmyth, K. A., 1982, Molecular genetics of yeast mating type, Annu. Rev. Genet. 16:439–500.
Pritchard, R., and Lark, K., 1984, Induction of replication by thymine starvation at the chromosome origin in E. coli, J. Mol. Biol. 9:288–307.
Rao, P. N., and Johnson, R. T., 1970, Mammalian cell fusion: Studies on the regulation of DNA synthesis and mitosis, Nature (London) 225:159–164.
Roberts, J., and Axel, R., 1982, Gene amplification and gene correction in somatic cells, Cell 29:109–119.
Roberts, J., and Weintraub, H., 1986, Negative control of DNA replication in composite SV40-bovine papilloma virus plasmids, Cell (in press).
Roberts, J., Buck, L., and Axel, R., 1983, A structure for amplified DNA, Cell 33:53–63.
Roman, A., and Dulbecco, R., 1975, Fate of polyoma form I DNA during replication, J. Virol. 16:70–74.
Sarver, N., Byrne, J. C., and Howley, P. M., 1982, 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. 79:7147–7151.
Sarver, N., Rabson, M. S., Yang, Y.-C., Byrne, J. C., and Howley, P. M., 1984, Localization and analysis of bovine papillomavirus type 1 transforming functions, J. Virol. 52:377–388.
Southern, P. J., and Berg, P., 1982, Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter, J. Mol. Appl. Genet. 1:327–341.
Spalholz, B. A., Yang, Y. C, and Howley, P. M., 1985, Transactivation of a bovine papillomavirus transcriptional regulatory element by the E2 gene product, Cell 42:183–191.
Spradling, A., 1981, The origin and amplification of two chromosomal domains containing Drosophila chorion genes, Cell 27:193–201.
Stenlund, A., Zabielski, J., Ahola, H., Moreno-Lopez, J., and Petterson, U., 1985, The messenger RNAs from the transforming region of bovine papillomavirus type 1, J. Mol. Biol. 182:541–554.
Tegtmeyer, P., 1972, Simian virus 40 deoxyribonucleic acid synthesis: The viral replicon, J. Virol. 10:591–598.
Tjian, R., 1978, The binding site on SV40 DNA for a T antigen-related protein, Cell 13:165–180.
Tlsty, T., Brown, P., and Schimke, R., 1984, UV radiation facilitates methotrexate resistance and amplification of the dihydrofolate reductase gene in cultured 3T6 mouse cells, Mol. Cell. Biol. 4:1050–1056.
Tsui, L.-C., Breitman, M. L., Siminovitch, L., and Buchwald, M., 1982, Persistence of freely replicating SV40 recombinant molecules carrying a selectable marker in permissive simian cells, Cell 30:499–508.
Varshavsky, A., 1981, On the possibility of metabolic control of replicon “mis-firing”: Relationship to emergence of malignant phenotypes in mammalian cell lineages, Proc. Natl. Acad. Sci. U.S.A. 78:3673–3677.
Waldeck, W., Rosel, F., and Dengraf, H., 1984, Origin of replication in episomal bovine papilloma virus type I DNA isolated from transformed cell, EMBO J. 31:2173–2178.
Woodcock, D., and Cooper, I., 1981, Evidence for double replication of chromosomal DNA segments as a general consequence of DNA replication inhibition, Cancer Res. 41:2483–2490.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1987 Plenum Press, New York
About this chapter
Cite this chapter
Roberts, J.M., Weintraub, H. (1987). Negative Control of DNA Replication Revealed in Composite Simian Virus 40-Bovine Papillomavirus Plasmids. In: Poste, G., Crooke, S.T. (eds) New Frontiers in the Study of Gene Functions. New Horizons in Therapeutics. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1845-3_3
Download citation
DOI: https://doi.org/10.1007/978-1-4613-1845-3_3
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-9030-8
Online ISBN: 978-1-4613-1845-3
eBook Packages: Springer Book Archive