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Increase of extrachromosomal circular DNA in mouse 3T6 cells on perturbation of DNA synthesis: Implications for gene amplification

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Somatic Cell and Molecular Genetics

Abstract

We have analyzed the amount of extrachromosomal double-stranded covalently closed circular nonmitochondrial DNA in mouse 3T6 cells by Southern blotting and electron microscopy. Treatment with 7,1-dimethylbenz[a] anthracene, known to promote amplification of integrated SV40 genomes, elevated the amount of circular DNA. Inhibition of DNA synthesis with hydroxyurea, earlier shown to enhance amplification of the cellular dihydrofolate reductase gene, resulted in yet higher levels. Thus, elevation of the frequency of gene amplification and generation of extrachromosomal circular DNA seem to accompany each other in the situations studied in this paper. Two other DNA synthesis inhibitors, aphidicolin and thymidine, had markedly lesser effects on circular DNA. The significance of these findings for the mechanism of gene amplification is discussed.

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Author notes

  1. Per Sunnerhagen

    Present address: Department of Biology, University of California, 92093, San Diego, La Jolla, California

Authors and Affiliations

  1. Department of Medical Biochemistry, University of Göteborg, P.O. Box 33031, S-400 33, Göteborg, Sweden

    Per Sunnerhagen, Rose-Marie Sjöberg & Gunnar Bjursell

Authors
  1. Per Sunnerhagen
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  2. Rose-Marie Sjöberg
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  3. Gunnar Bjursell
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Sunnerhagen, P., Sjöberg, RM. & Bjursell, G. Increase of extrachromosomal circular DNA in mouse 3T6 cells on perturbation of DNA synthesis: Implications for gene amplification. Somat Cell Mol Genet 15, 61–70 (1989). https://doi.org/10.1007/BF01534670

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  • DOI: https://doi.org/10.1007/BF01534670

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