Response of ataxia telangiectasia cells to restriction endonuclease induced DNA double-strand breaks: I. Cytogenetic characterization.

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.

• Authors: N Liu, P E Bryant
• Journal: Mutagenesis (Mutagenesis) Vol. 8 Issue 6 Pg. 503-10 (Nov 1993) ISSN: 0267-8357 [Print] England
• PMID: 8133779 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Streptolysins
• streptolysin O
• DNA
• Deoxyribonuclease BamHI
• CAGCTG-specific type II deoxyribonucleases
• Deoxyribonucleases, Type II Site-Specific

Topics

• Ataxia Telangiectasia (pathology)
• Bacterial Proteins
• Cell Membrane Permeability (drug effects)
• Cells, Cultured
• Chromosome Aberrations
• DNA (drug effects, radiation effects)
• DNA Damage
• Deoxyribonuclease BamHI (pharmacology)
• Deoxyribonucleases, Type II Site-Specific (pharmacology)
• Humans
• Lymphocytes (drug effects, radiation effects, ultrastructure)
• Micronucleus Tests
• Streptolysins (pharmacology)