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Partial complementation of the Fanconi anemia defect upon transfection by heterologous DNA

Phenotypic dissociation of chromosomal and cellular hypersensitivity to DNA cross-linking agents

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Summary

Transfectants obtained by mouse DNA-mediated gene transfer in Fanconi anemia (FA) primary fibroblasts from the genetic complementation groups A and B were examined for the frequencies of chromosomal aberrations and cytotoxicity following treatments by cross-linking agents. Cells from group A (FA 150), which is the most sensitive to such agents, are partially corrected for both the chromosomal and cellular hypersensitivity to 8-methoxypsoralen photoaddition. In contrast, after treatment with mitomycin C (MMC), only the chromosomal sensitivity is re-established to a near normal level. The opposite is true for FA group B cells (FA 145), i.e. cell survival to MMC is partially corrected, whereas the frequency of MMC-induced chromosomal aberration remains close to that of the untransfected cells. The partial phenotypic correction of the two end points examined is interpreted as indicating either a gene dosage effect or the necessity of introducing more than one gene type in order to achieve complete recovery of a normal phenotype. The phenotypic dissociation between the clastogenic and cellular hypersensitivity to crosslinking agents may offer the opportunity of isolating separately the responsible gene(s) by conventional rescue techniques.

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Authors and Affiliations

  1. CNRS URA 1292, Institut Curie, Biologie, 26, Rue d'Ulm, F-75231, Paris Cedex 05, France

    C. Diatloff-Zito, F. Rosselli, J. Heddle & E. Moustacchi

  2. Dipartimento di Scienze dell'Ambiente e del Territorio, Genetica, Università di Pisa, Via S. Giuseppe, 22, I-56100, Pisa, Italy

    F. Rosselli

  3. Department of Biology, York University, 4700 Keele Street, M3J 1P3, Toronto, Ontario, Canada

    J. Heddle

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  1. C. Diatloff-Zito
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  2. F. Rosselli
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  3. J. Heddle
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  4. E. Moustacchi
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Diatloff-Zito, C., Rosselli, F., Heddle, J. et al. Partial complementation of the Fanconi anemia defect upon transfection by heterologous DNA. Hum Genet 86, 151–161 (1990). https://doi.org/10.1007/BF00197697

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  • DOI: https://doi.org/10.1007/BF00197697

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