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  • Title: Response of ataxia telangiectasia cells to restriction endonuclease induced DNA double-strand breaks: I. Cytogenetic characterization.
    Author: Liu N, Bryant PE.
    Journal: Mutagenesis; 1993 Nov; 8(6):503-10. PubMed ID: 8133779.
    Abstract:
    Ataxia telangiectasia (AT) and normal human lymphoblastoid cell lines have been treated with either X-rays or the restriction endonucleases PvuII and BamHI using streptolysin-O poration, and the frequencies of micronuclei or chromosomal aberrations measured. We report that AT cells (AT-PA) are hypersensitive to the restriction endonucleases PvuII and BamHI, inducing DNA double-strand breaks (dsb) with either blunt or cohesive termini, respectively. Our data indicates that AT-PA cells have a dsb processing defect that leads to a higher rate of conversion of dsb into chromosomal aberrations than in normal cells. AT-PA cells showed up to a 5-fold enhanced sensitivity to PvuII over the normal (N-SW) line, a result of an increase in frequencies of chromatid aberrations. Chromosome-type aberrations appeared not to be increased in AT-PA cells over those induced in the normal N-SW line. Particularly striking was the appearance in AT-PA of high frequencies of chromatid aberrations at the 24 h sampling time. BamHI also caused enhanced aberration frequencies in AT-PA cells although the cohesive-ended dsb caused by BamHI still appeared to be less effective in causing chromosomal aberrations than the blunt-ended dsb caused by PvuII in both AT-PA and N-SW, as we have previously reported for Chinese hamster cells. The enhanced effectiveness of cohesive-ended dsb in AT-PA cells over normal cells may be a result of altered processing of dsb by AT-PA cells or may be caused by conversion of some cohesive-ended dsb into blunt-ended dsb by exonuclease digestion before ligation can take place.
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