Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1988 Mar 25;16(5 Pt B):2313–2322. doi: 10.1093/nar/16.5.2313

Heteroduplex-induced mutagenesis in mammalian cells.

U Weiss 1, J H Wilson 1
PMCID: PMC338218  PMID: 2833731

Abstract

We have shown previously that heteroduplexes containing single-stranded loops are repaired efficiently in monkey cells, but not always correctly: 2% of the repair products acquired mutations within a 350 base-pair target (Weiss, U. and Wilson, J.H., Proc. Natl. Acad. Sci. USA 87:1123-1126, 1987). The structures of the mutant genomes, which are described here, are consistent with an error-prone repair system. The spectrum of mutations includes about 25% point mutations and 75% rearrangements, which consist of deletions, duplications, and substitutions. The mutations are clustered in the vicinity of single-stranded loops in the original heteroduplex. The high frequency of mutation, their clustering, and the positions of rearrangement endpoints suggest that the mutations were generated during repair of the heteroduplexes.

Full text

PDF
2313

Selected References

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

  1. Bianchi M. E., Radding C. M. Insertions, deletions and mismatches in heteroduplex DNA made by recA protein. Cell. 1983 Dec;35(2 Pt 1):511–520. doi: 10.1016/0092-8674(83)90185-x. [DOI] [PubMed] [Google Scholar]
  2. Folger K. R., Thomas K., Capecchi M. R. Efficient correction of mismatched bases in plasmid heteroduplexes injected into cultured mammalian cell nuclei. Mol Cell Biol. 1985 Jan;5(1):70–74. doi: 10.1128/mcb.5.1.70. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Hamza H., Kalogeropoulos A., Nicolas A., Rossignol J. L. Two mechanisms for directional gene conversion. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7386–7390. doi: 10.1073/pnas.83.19.7386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hauser J., Seidman M. M., Sidur K., Dixon K. Sequence specificity of point mutations induced during passage of a UV-irradiated shuttle vector plasmid in monkey cells. Mol Cell Biol. 1986 Jan;6(1):277–285. doi: 10.1128/mcb.6.1.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Lichten M., Fox M. S. Effects of nonhomology on bacteriophage lambda recombination. Genetics. 1983 Jan;103(1):5–22. doi: 10.1093/genetics/103.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lichten M., Fox M. S. Evidence for inclusion of regions of nonhomology in heteroduplex products of bacteriophage lambda recombination. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7180–7184. doi: 10.1073/pnas.81.22.7180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Meselson M. S., Radding C. M. A general model for genetic recombination. Proc Natl Acad Sci U S A. 1975 Jan;72(1):358–361. doi: 10.1073/pnas.72.1.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Miller J. H., Lebkowski J. S., Greisen K. S., Calos M. P. Specificity of mutations induced in transfected DNA by mammalian cells. EMBO J. 1984 Dec 20;3(13):3117–3121. doi: 10.1002/j.1460-2075.1984.tb02267.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Orr-Weaver T. L., Szostak J. W. Fungal recombination. Microbiol Rev. 1985 Mar;49(1):33–58. doi: 10.1128/mr.49.1.33-58.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Radding C. M. Genetic recombination: strand transfer and mismatch repair. Annu Rev Biochem. 1978;47:847–880. doi: 10.1146/annurev.bi.47.070178.004215. [DOI] [PubMed] [Google Scholar]
  12. Roth D. B., Porter T. N., Wilson J. H. Mechanisms of nonhomologous recombination in mammalian cells. Mol Cell Biol. 1985 Oct;5(10):2599–2607. doi: 10.1128/mcb.5.10.2599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Roth D. B., Wilson J. H. Nonhomologous recombination in mammalian cells: role for short sequence homologies in the joining reaction. Mol Cell Biol. 1986 Dec;6(12):4295–4304. doi: 10.1128/mcb.6.12.4295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sarkar S., Dasgupta U. B., Summers W. C. Error-prone mutagenesis detected in mammalian cells by a shuttle vector containing the supF gene of Escherichia coli. Mol Cell Biol. 1984 Oct;4(10):2227–2230. doi: 10.1128/mcb.4.10.2227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Seidman M. M., Bredberg A., Seetharam S., Kraemer K. H. Multiple point mutations in a shuttle vector propagated in human cells: evidence for an error-prone DNA polymerase activity. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4944–4948. doi: 10.1073/pnas.84.14.4944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Seidman M. M., Dixon K., Razzaque A., Zagursky R. J., Berman M. L. A shuttle vector plasmid for studying carcinogen-induced point mutations in mammalian cells. Gene. 1985;38(1-3):233–237. doi: 10.1016/0378-1119(85)90222-7. [DOI] [PubMed] [Google Scholar]
  17. Szostak J. W., Orr-Weaver T. L., Rothstein R. J., Stahl F. W. The double-strand-break repair model for recombination. Cell. 1983 May;33(1):25–35. doi: 10.1016/0092-8674(83)90331-8. [DOI] [PubMed] [Google Scholar]
  18. Thimmappaya B., Shenk T. Nucleotide sequence analysis of viable deletion mutants lacking segments of the simian virus 40 genome coding for small t antigen. J Virol. 1979 Jun;30(3):668–673. doi: 10.1128/jvi.30.3.668-673.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Thomas K. R., Capecchi M. R. Introduction of homologous DNA sequences into mammalian cells induces mutations in the cognate gene. Nature. 1986 Nov 6;324(6092):34–38. doi: 10.1038/324034a0. [DOI] [PubMed] [Google Scholar]
  20. Van Heuverswyn H., Fiers W. Nucleotide sequence of the Hind-C fragment of simian virus 40 DNA. Comparison of the 5'-untranslated region of wild-type virus and of some deletion Mutants. Eur J Biochem. 1979 Oct;100(1):51–60. doi: 10.1111/j.1432-1033.1979.tb02032.x. [DOI] [PubMed] [Google Scholar]
  21. Weiss U., Wilson J. H. Repair of single-stranded loops in heteroduplex DNA transfected into mammalian cells. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1619–1623. doi: 10.1073/pnas.84.6.1619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. White J. H., Lusnak K., Fogel S. Mismatch-specific post-meiotic segregation frequency in yeast suggests a heteroduplex recombination intermediate. Nature. 1985 May 23;315(6017):350–352. doi: 10.1038/315350a0. [DOI] [PubMed] [Google Scholar]
  23. White R. L., Fox M. S. On the molecular basis of high negative interference. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1544–1548. doi: 10.1073/pnas.71.4.1544. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES