James Ford

Publication Details

  • LI-FRAUMENI SYNDROME FIBROBLASTS HOMOZYGOUS FOR P53 MUTATIONS ARE DEFICIENT IN GLOBAL DNA-REPAIR BUT EXHIBIT NORMAL TRANSCRIPTION-COUPLED REPAIR AND ENHANCED UV RESISTANCE PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Ford, J. M., Hanawalt, P. C. 1995; 92 (19): 8876-8880

    Abstract:

    We investigated whether mutations in the p53 tumor suppressor gene alter UV sensitivity and/or repair of UV-induced DNA damage in primary human skin fibroblasts from patients with Li-Fraumeni syndrome, heterozygous for mutations in one allele of the p53 gene (p53 wt/mut) and sublines expressing only mutant p53 (p53 mut). The p53 mut cells were more resistant than the p53 wt/mut cells to UV cytotoxicity and exhibited less UV-induced apoptosis. DNA repair analysis revealed reduced removal of cyclobutane pyrimidine dimers from overall genomic DNA in vivo in p53 mut cells compared with p53 wt/mut or normal cells. However, p53 mut cells retained the ability to preferentially repair damage in the transcribed strands of expressed genes (transcription-coupled repair). These results suggest that loss of p53 function may lead to greater genomic instability by reducing the efficiency of DNA repair but that cellular resistance to DNA-damaging agents may be enhanced through elimination of apoptosis.

    View details for Web of Science ID A1995RU75900070

    View details for PubMedID 7568035

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