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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Apr;79(8):2641–2644. doi: 10.1073/pnas.79.8.2641

Genetic heterogeneity in ataxia-telangiectasia studied by cell fusion.

N G Jaspers, D Bootsma
PMCID: PMC346256  PMID: 6953420

Abstract

The effect of x-rays on the rate of semiconservative DNA replication was investigated by autoradiography in single cells obtained from normal individuals and from patients having ataxia-telangiectasia (AT). In the five AT cell strains studied, the rate of DNA synthesis was inhibited to a lesser extent that in two normal cell strains. By using this abnormal regulation of DNA replication in AT cells as a marker, an experimental procedure was developed that allowed genetic complementation analysis of AT. After Sendai virus-induced fusion of AT cells, the grains were counted over binucleate cells with both nuclei in S phase. In some cases, the inhibition of DNA synthesis caused by x-rays in the heterodikaryons was more pronounced than that in the parental homodikaryons and was comparable to that in normal binucleate cells, indicating complementation. By using this approach, the five AT cell strains that were investigated could be assigned to three complementation groups. The data suggest that extensive genetic heterogeneity exists in AT.

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Selected References

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

  1. Edwards M. J., Taylor A. M. Unusual levels of (ADP-ribose)n and DNA synthesis in ataxia telangiectasia cells following gamma-ray irradiation. Nature. 1980 Oct 23;287(5784):745–747. doi: 10.1038/287745a0. [DOI] [PubMed] [Google Scholar]
  2. Houldsworth J., Lavin M. F. Effect of ionizing radiation on DNA synthesis in ataxia telangiectasia cells. Nucleic Acids Res. 1980 Aug 25;8(16):3709–3720. doi: 10.1093/nar/8.16.3709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Jaspers N. G., Jansen-van de Kuilen G., Bootsma D. Complement analysis of xeroderma pigmentosum variants. Exp Cell Res. 1981 Nov;136(1):81–90. doi: 10.1016/0014-4827(81)90039-2. [DOI] [PubMed] [Google Scholar]
  4. Keijzer W., Jaspers N. G., Abrahams P. J., Taylor A. M., Arlett C. F., Zelle B., Takebe H., Kinmont P. D., Bootsma D. A seventh complementation group in excision-deficient xeroderma pigmentosum. Mutat Res. 1979 Aug;62(1):183–190. doi: 10.1016/0027-5107(79)90231-8. [DOI] [PubMed] [Google Scholar]
  5. Painter R. B., Young B. R. Radiosensitivity in ataxia-telangiectasia: a new explanation. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7315–7317. doi: 10.1073/pnas.77.12.7315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Paterson M. C., Smith B. P., Lohman P. H., Anderson A. K., Fishman L. Defective excision repair of gamma-ray-damaged DNA in human (ataxia telangiectasia) fibroblasts. Nature. 1976 Apr 1;260(5550):444–447. doi: 10.1038/260444a0. [DOI] [PubMed] [Google Scholar]
  7. Paterson M. C., Smith P. J. Ataxia telangiectasia: an inherited human disorder involving hypersensitivity to ionizing radiation and related DNA-damaging chemicals. Annu Rev Genet. 1979;13:291–318. doi: 10.1146/annurev.ge.13.120179.001451. [DOI] [PubMed] [Google Scholar]
  8. Rudé J. M., Friedberg E. C. Semi-conservative deoxyribonucleic acid synthesis in unirradiated and ultraviolet-irradiated xeroderma pigmentosum and normal human skin fibroblasts. Mutat Res. 1977 Mar;42(3):433–442. doi: 10.1016/s0027-5107(77)80047-x. [DOI] [PubMed] [Google Scholar]
  9. de Wit J., Jaspers N. G., Bootsma D. The rate of DNA synthesis in normal human and ataxia telangiectasia cells after exposure to X-irradiation. Mutat Res. 1981 Jan;80(1):221–226. doi: 10.1016/0027-5107(81)90190-1. [DOI] [PubMed] [Google Scholar]

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