Journal Article

Deficiency in the repair of UV-induced DNA damage in human skin fibroblasts compromised for the <i>ATM</i> gene

Mohammed A. Hannan, Ali Hellani, Fahad M. Al-Khodairy, Mohammed Kunhi, Yunis Siddiqui, Noujud Al-Yussef, Nancy Pangue-Cruz, Monica Siewertsen, Mohammed N. Al-Ahdal and Abdelilah Aboussekhra

in Carcinogenesis

Volume 23, issue 10, pages 1617-1624
Published in print October 2002 | ISSN: 0143-3334
Published online October 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.10.1617
Deficiency in the repair of UV-induced DNA damage in human skin fibroblasts compromised for the ATM gene

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Ataxia-telangiectasia (A-T), is an autosomal recessive disease characterized by neurological and immunological symptoms, radiosensitivity and cancer predisposition. A-T cells exhibit a greatly decreased survival and a reduction in DNA synthesis inhibition as well as p53 induction in response to ionizing radiation. Occasionally, some strains of A-T cells have been reported to manifest a slightly enhanced sensitivity with no consistent observations of a deficiency in either cell cycle control or the repair of DNA damage after treatment with ultraviolet (UV) light. In the present study it is shown that skin fibroblasts from four A-T patients, compared with the control, display enhanced sensitivity to the killing effect of UV-light, moderate radioresistant DNA synthesis, and a reduction in viral recovery in the host cell reactivation (HCR) assay. PCR based analysis indicated that three of these UV-sensitive A-T cell strains bear a large deletion in the ATM gene, and no ATM polypeptide was detected in their cell free extracts. Moreover, it is shown that, in non-replicative conditions, these A-T cells are less efficient than normal cells in repairing the T4 endonuclease V sensitive sites. These results constitute the first clear evidence showing the deficiency of A-T cells in the repair of UV-induced DNA damage, and provide further information on the relationship between cell cycle control and DNA repair in human cells.

Keywords: A-T, ataxia-telangiectasia; CPDs, cyclobutane pyrimidine dimers; EMEM, Eagle’s minimal essential medium; HCR, host cell reactivation; HSV, herpes simplex virus; IR, ionizing radiation; LZ, leucine zipper; NER, nucleotide excision repair; P1-3 K, phosphatidylinositol-3 kinase; RDS, radioresistant DNA synthesis; UDS, unscheduled DNA synthesis.

Journal Article.  6129 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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