Abstract

Gene therapy has been hindered by the low frequency of homologous recombination in mammalian cells. To stimulate recombination, we investigated the use of triple-helix-forming oligonucleotides (TFOs) to target DNA damage to a selected site within cells. By treating cells with TFOs linked to psoralen, recombination was induced within a simian virus 40 vector carrying two mutant copies of the supF tRNA reporter gene. Gene conversion events, as well as mutations at the target site, were also observed. The variety of products suggests that multiple cellular pathways can act on the targeted damage, and data showing that the triple helix can influence these pathways are presented. The ability to specifically induce recombination or gene conversion within mammalian cells by using TFOs may provide a new research tool and may eventually lead to novel applications in gene therapy.

Keywords

BiologyHomologous recombinationGene conversionGene targetingMutantGeneReporter geneDNA damageOligonucleotideDNAMutationTriple helixRecombinationMolecular biologyGeneticsGene expression

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Publication Info

Year
1996
Type
article
Volume
16
Issue
12
Pages
6820-6828
Citations
102
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Closed

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A. Fawad Faruqi, Michael M. Seidman, David J. Segal et al. (1996). Recombination Induced by Triple-Helix-Targeted DNA Damage in Mammalian Cells. Molecular and Cellular Biology , 16 (12) , 6820-6828. https://doi.org/10.1128/mcb.16.12.6820

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DOI
10.1128/mcb.16.12.6820