Biopolym. Cell. 1999; 15(1):57-62.
Molecular Mechanisms of Differentiation
Modification of the DNA structure of plasmid pATV-8 in transgenic mice. 3. Analysis of nucleotide sequence of the extrachromosomal transient, and it's replication in insect cells
1Krysan K. V., 1Kikhno I. M., 1Strokovskaya L. I., 1Solomko A. P.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680


We have determined the nucleotide sequence of the mwine extrachromosomal transgene. Analysis of DNA sequences, which were generated by rearrangements of the primary injected plasmid, revealed high homology with consensus sequence for eukaryotic ori replication,. Most probably, due to these sequences transgene has gained the ability to replicate in mouse cells. We have also demonstrated, that given transgene is able to replicate in the insect cells.


[1] Cuzin F, Vogt M, Dieckmann M, Berg P. Induction of virus multiplication in 3T3 cells transformed by a thermosensitive mutant of polyoma virus. II. Formation of oligometric polyoma DNA molecules. J Mol Biol. 1970;47(3):317-33.
[2] Rassoulzadegan M, Leopold P, Vailly J, Cuzin F. Germ line transmission of autonomous genetic elements in transgenic mouse strains. Cell. 1986;46(4):513-9.
[3] Moses K, Prives C. A unique subpopulation of murine DNA polymerase alpha/primase specifically interacts with polyomavirus T antigen and stimulates DNA replication. Mol Cell Biol. 1994;14(4):2767-76.
[4] Eki T, Enomoto T, Masutani C, Miyajima A, Takada R, Murakami Y, Ohno T, Hanaoka F, Ui M. Mouse DNA primase plays the principal role in determination of permissiveness for polyomavirus DNA replication. J Virol. 1991;65(9):4874-81.
[5] Calos MP, Lebkowski JS, Botchan MR. High mutation frequency in DNA transfected into mammalian cells. Proc Natl Acad Sci USA. 1983;80(10):3015-9.
[6] Razzaque A, Mizusawa H, Seidman MM. Rearrangement and mutagenesis of a shuttle vector plasmid after passage in mammalian cells. Proc Natl Acad Sci USA. 1983;80(10):3010-4.
[7] Gilbert DM, Cohen SN. Bovine papilloma virus plasmids replicate randomly in mouse fibroblasts throughout S phase of the cell cycle. Cell. 1987;50(1):59-68.
[8] Ten Hagen KG, Ravnan JB, Cohen SN. Disparate replication properties of integrated and extrachromosomal forms of bovine papilloma virus in ID13 cells. J Mol Biol. 1995;254(2):119-29.
[9] Nikolaev AI, Tchkonia TT, Eristavi-Kafiani KA, Tarantyl VZ. Analysis of rescued plasmid from the transgenic silkworm. Biopolym. Cell. 1992; 8(3):29-32
[10] Nikolaev AI, Tchkonia TT, Kafiani-Eristavi KA. Extrachromosomal lokalization and transmittance of the recombinant plasmid, migroinjected into the silkworm grain. Mol Biol (Mosk). 1991; 25(5): 1136-45.
[11] Newlon CS, Theis JF. The structure and function of yeast ARS elements. Curr Opin Genet Dev. 1993;3(5):752-8.
[12] Sohn JH, Choi ES, Kim CH, Agaphonov MO, Ter-Avanesyan MD, Rhee JS, Rhee SK. A novel autonomously replicating sequence (ARS) for multiple integration in the yeast Hansenula polymorpha DL-1. J Bacteriol. 1996;178(15):4420-8.
[13] Roth GE.Replication analysis of plasmid DNAs injected into Drosophila embryos. Chromosoma. 1991;100(4):267-77.
[14] Masukata H, Satoh H, Obuse C, Okazaki T. Autonomous replication of human chromosomal DNA fragments in human cells. Mol Biol Cell. 1993;4(11):1121-32.
[15] Taira T, Iguchi-Ariga SM, Ariga H. A novel DNA replication origin identified in the human heat shock protein 70 gene promoter. Mol Cell Biol. 1994;14(9):6386-97.
[16] Carroll SM, Gaudray P, De Rose ML, Emery JF, Meinkoth JL, Nakkim E, Subler M, Von Hoff DD, Wahl GM. Characterization of an episome produced in hamster cells that amplify a transfected CAD gene at high frequency: functional evidence for a mammalian replication origin. Mol Cell Biol. 1987;7(5):1740-50.
[17] Donovan S, Diffley JF. Replication origins in eukaroytes. Curr Opin Genet Dev. 1996;6(2):203-7.
[18] Vasetskii ES, Razin SV. Cells of higher eukaryotes contain proteins, interacting with yeast autonomously replicating sequence (ARS). Dokl Akad Nauk. 1993;330(1):111-2.
[19] Katz RA, Omer CA, Weis JH, Mitsialis SA, Faras AJ, Guntaka RV. Restriction endonuclease and nucleotide sequence analyses of molecularly cloned unintegrated avian tumor virus DNA: structure of large terminal repeats in circle junctions. J Virol. 1982;42(1):346-51.
[20] Solomko AP, Ryndich AV, Titok TG, Morozova LM, Vagina IN, Chashchina LI, Evsykov SV, Kirichenko IV, Sarapina NA. The transgenic mice containing pATV-8 AND pBR322 plasmids. Biopolym. Cell. 1988;4(5):267-269
[21] Chashchina LI, Krysan KV, Matkovsky VI, Solomko AP. Structure rearrangement of plasmid pATV8 in transgenic mice. 2. Physical mapping of autonomous transgenome and sequencing of cloned fragment of its modified region. Biopolym. Cell. 1997; 13(5):397-402
[22] Makino Y, Kanno R, Koseki H, Taniguchi M. Development of Valpha4+ NK T cells in the early stages of embryogenesis. Proc Natl Acad Sci USA. 1996;93(13):6516-20.
[23] Brykov VA, Kukhlevskii AD. Relation between changes in the palindromic fraction and DNA replication during early stages of sea urchin development. Mol Biol (Mosk). 1988;22(2):377-83.
[24] Gibbs M1, Collick A, Kelly RG, Jeffreys AJ. A tetranucleotide repeat mouse minisatellite displaying substantial somatic instability during early preimplantation development. Genomics. 1993;17(1):121-8.
[25] Kelly RG. Similar origins of two mouse minisatellites within transposon-like LTRs. Genomics. 1994;24(3):509-15.
[26] Sal'nokov KV. Extrachromosomal DNA in mammalian cells. Tsitologiia. 1990;32(11):1061-71.
[27] Johnson EM, Jelinek WR. Replication of a plasmid bearing a human Alu-family repeat in monkey COS-7 cells. Proc Natl Acad Sci USA. 1986;83(13):4660-4.
[28] Goldberg EZ, Naroditsky BS, Felgenhauer PE, Garaev MM, Tikchonenko TI. Replication of heterologous DNA in Xenopus laevis oocytes. FEBS Lett. 1981;124(2):215-8.