Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1986 Nov;6(11):3920–3927. doi: 10.1128/mcb.6.11.3920

New class of polyomavirus mutant that can persist as free copies in F9 embryonal carcinoma cells.

K Ariizumi, H Ariga
PMCID: PMC367155  PMID: 3025619

Abstract

A small circular DNA was found extrachromosomally in a clone of F9 embryonal carcinoma (EC) cells at high copy numbers per cell. The DNA was cloned in plasmid pUC19. Restriction endonuclease analyses of the DNA indicated that the DNA (fPyF9) was a mutant of polyomavirus (Py) DNA and had a mutation in a noncoding regulatory region. There have been many reports on the isolation of Py mutants capable of replication in undifferentiated cells. However, fPyF9 was different from other Py mutants in the following aspects: it was harbored stably as a free copy at 1 X 10(4) to 5 X 10(4) copies per cell in EC cells; it replicated in undifferentiated cells better than in differentiated cells; it was extremely rearranged in the sequences of the enhancer B domain; and it carried in the enhancer B domain three copies of an exogenous sequence which does not exist in Py strain A2. From these observations, we propose a new class of Py EC mutant which has an autonomous state similar to that of plasmid and small circular DNA in host cells.

Full text

PDF
3927

Images in this article

Selected References

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

  1. Amati P. Polyoma regulatory region: a potential probe for mouse cell differentiation. Cell. 1985 Dec;43(3 Pt 2):561–562. doi: 10.1016/0092-8674(85)90225-9. [DOI] [PubMed] [Google Scholar]
  2. Benoist C., Chambon P. In vivo sequence requirements of the SV40 early promotor region. Nature. 1981 Mar 26;290(5804):304–310. doi: 10.1038/290304a0. [DOI] [PubMed] [Google Scholar]
  3. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blin N., Stafford D. W. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. doi: 10.1093/nar/3.9.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Böhnlein E., Chowdhury K., Gruss P. Functional analysis of the regulatory region of polyoma mutant F9-1 DNA. Nucleic Acids Res. 1985 Jul 11;13(13):4789–4809. doi: 10.1093/nar/13.13.4789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Calabretta B., Robberson D. L., Barrera-Saldaña H. A., Lambrou T. P., Saunders G. F. Genome instability in a region of human DNA enriched in Alu repeat sequences. Nature. 1982 Mar 18;296(5854):219–225. doi: 10.1038/296219a0. [DOI] [PubMed] [Google Scholar]
  7. De Simone V., La Mantia G., Lania L., Amati P. Polyomavirus mutation that confers a cell-specific cis advantage for viral DNA replication. Mol Cell Biol. 1985 Aug;5(8):2142–2146. doi: 10.1128/mcb.5.8.2142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Fujimura F. K., Deininger P. L., Friedmann T., Linney E. Mutation near the polyoma DNA replication origin permits productive infection of F9 embryonal carcinoma cells. Cell. 1981 Mar;23(3):809–814. doi: 10.1016/0092-8674(81)90445-1. [DOI] [PubMed] [Google Scholar]
  10. Gelinas R. E., Myers P. A., Roberts R. J. Two sequence-specific endonucleases from Moraxella bovis. J Mol Biol. 1977 Jul;114(1):169–179. doi: 10.1016/0022-2836(77)90290-x. [DOI] [PubMed] [Google Scholar]
  11. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gorman C. M., Rigby P. W., Lane D. P. Negative regulation of viral enhancers in undifferentiated embryonic stem cells. Cell. 1985 Sep;42(2):519–526. doi: 10.1016/0092-8674(85)90109-6. [DOI] [PubMed] [Google Scholar]
  13. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  14. Hattman S., Brooks J. E., Masurekar M. Sequence specificity of the P1 modification methylase (M.Eco P1) and the DNA methylase (M.Eco dam) controlled by the Escherichia coli dam gene. J Mol Biol. 1978 Dec 15;126(3):367–380. doi: 10.1016/0022-2836(78)90046-3. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Hogan B. L., Taylor A., Adamson E. Cell interactions modulate embryonal carcinoma cell differentiation into parietal or visceral endoderm. Nature. 1981 May 21;291(5812):235–237. doi: 10.1038/291235a0. [DOI] [PubMed] [Google Scholar]
  18. Katinka M., Vasseur M., Montreau N., Yaniv M., Blangy D. Polyoma DNA sequences involved in control of viral gene expression in murine embryonal carcinoma cells. Nature. 1981 Apr 23;290(5808):720–722. doi: 10.1038/290720a0. [DOI] [PubMed] [Google Scholar]
  19. Katinka M., Yaniv M., Vasseur M., Blangy D. Expression of polyoma early functions in mouse embryonal carcinoma cells depends on sequence rearrangements in the beginning of the late region. Cell. 1980 Jun;20(2):393–399. doi: 10.1016/0092-8674(80)90625-x. [DOI] [PubMed] [Google Scholar]
  20. Krolewski J. J., Schindler C. W., Rush M. G. Structure of extrachromosomal circular DNAs containing both the Alu family of dispersed repetitive sequences and other regions of chromosomal DNA. J Mol Biol. 1984 Mar 25;174(1):41–54. doi: 10.1016/0022-2836(84)90364-4. [DOI] [PubMed] [Google Scholar]
  21. Kunisada T., Yamagishi H. Sequence repetition and genomic distribution of small polydisperse circular DNA purified from HeLa cells. Gene. 1984 Nov;31(1-3):213–223. doi: 10.1016/0378-1119(84)90212-9. [DOI] [PubMed] [Google Scholar]
  22. Lacks S., Greenberg B. A deoxyribonuclease of Diplococcus pneumoniae specific for methylated DNA. J Biol Chem. 1975 Jun 10;250(11):4060–4066. [PubMed] [Google Scholar]
  23. Lehman J. M., Speers W. C., Swartzendruber D. E., Pierce G. B. Neoplastic differentiation: characteristics of cell lines derived from a murine teratocarcinoma. J Cell Physiol. 1974 Aug;84(1):13–27. doi: 10.1002/jcp.1040840103. [DOI] [PubMed] [Google Scholar]
  24. Lusky M., Berg L., Weiher H., Botchan M. Bovine papilloma virus contains an activator of gene expression at the distal end of the early transcription unit. Mol Cell Biol. 1983 Jun;3(6):1108–1122. doi: 10.1128/mcb.3.6.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Luthman H., Nilsson M. G., Magnusson G. Non-contiguous segments of the polyoma genome required in cis for DNA replication. J Mol Biol. 1982 Nov 15;161(4):533–550. doi: 10.1016/0022-2836(82)90406-5. [DOI] [PubMed] [Google Scholar]
  26. Maione R., Passananti C., De Simone V., Delli-Bovi P., Augusti-Tocco G., Amati P. Selection of mouse neuroblastoma cell-specific polyoma virus mutants with stage differentiative advantages of replication. EMBO J. 1985 Dec 1;4(12):3215–3221. doi: 10.1002/j.1460-2075.1985.tb04068.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Melin F., Pinon H., Reiss C., Kress C., Montreau N., Blangy D. Common features of polyomavirus mutants selected on PCC4 embryonal carcinoma cells. EMBO J. 1985 Jul;4(7):1799–1803. doi: 10.1002/j.1460-2075.1985.tb03853.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mintz B., Fleischman R. A. Teratocarcinomas and other neoplasms as developmental defects in gene expression. Adv Cancer Res. 1981;34:211–278. doi: 10.1016/s0065-230x(08)60243-2. [DOI] [PubMed] [Google Scholar]
  29. Myers R. M., Rio D. C., Robbins A. K., Tjian R. SV40 gene expression is modulated by the cooperative binding of T antigen to DNA. Cell. 1981 Aug;25(2):373–384. doi: 10.1016/0092-8674(81)90056-8. [DOI] [PubMed] [Google Scholar]
  30. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Schöler H. R., Gruss P. Specific interaction between enhancer-containing molecules and cellular components. Cell. 1984 Feb;36(2):403–411. doi: 10.1016/0092-8674(84)90233-2. [DOI] [PubMed] [Google Scholar]
  33. Sekikawa K., Levine A. J. Isolation and characterization of polyoma host range mutants that replicate in nullipotential embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1100–1104. doi: 10.1073/pnas.78.2.1100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Smith C. A., Vinograd J. Small polydisperse circular DNA of HeLa cells. J Mol Biol. 1972 Aug 21;69(2):163–178. doi: 10.1016/0022-2836(72)90222-7. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Strickland S., Mahdavi V. The induction of differentiation in teratocarcinoma stem cells by retinoic acid. Cell. 1978 Oct;15(2):393–403. doi: 10.1016/0092-8674(78)90008-9. [DOI] [PubMed] [Google Scholar]
  37. Swartzendruber D. E., Lehman J. M. Neoplastic differentiation: interaction of simian virus 40 and polyoma virus with murine teratocarcinoma cells in vitro. J Cell Physiol. 1975 Apr;85(2 Pt 1):179–187. doi: 10.1002/jcp.1040850204. [DOI] [PubMed] [Google Scholar]
  38. Tanaka K., Chowdhury K., Chang K. S., Israel M., Ito Y. Isolation and characterization of polyoma virus mutants which grow in murine embryonal carcinoma and trophoblast cells. EMBO J. 1982;1(12):1521–1527. doi: 10.1002/j.1460-2075.1982.tb01349.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Tyndall C., La Mantia G., Thacker C. M., Favaloro J., Kamen R. A region of the polyoma virus genome between the replication origin and late protein coding sequences is required in cis for both early gene expression and viral DNA replication. Nucleic Acids Res. 1981 Dec 11;9(23):6231–6250. doi: 10.1093/nar/9.23.6231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Vasseur M., Kress C., Montreau N., Blangy D. Isolation and characterization of polyoma virus mutants able to develop in embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1068–1072. doi: 10.1073/pnas.77.2.1068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Vigneron M., Barrera-Saldana H. A., Baty D., Everett R. E., Chambon P. Effect of the 21-bp repeat upstream element on in vitro transcription from the early and late SV40 promoters. EMBO J. 1984 Oct;3(10):2373–2382. doi: 10.1002/j.1460-2075.1984.tb02142.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. de Villiers J., Schaffner W. A small segment of polyoma virus DNA enhances the expression of a cloned beta-globin gene over a distance of 1400 base pairs. Nucleic Acids Res. 1981 Dec 11;9(23):6251–6264. doi: 10.1093/nar/9.23.6251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. de Villiers J., Schaffner W., Tyndall C., Lupton S., Kamen R. Polyoma virus DNA replication requires an enhancer. Nature. 1984 Nov 15;312(5991):242–246. doi: 10.1038/312242a0. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES