Responses of radiosensitive repair-proficient cell lines to restriction endonucleases

Radiosensitive mutant mammalian cell lines fall into two categories: (1) those exhibiting a deficiency in the rejoining of dsb, e.g. Chinese hamster xrs and XR1, and murine scid cells; and (2) those exhibiting apparently normal rejoining of bulk dsb, e.g. hamster irs mutants and cells from ataxia-telangiectasia individuals. Cells of both types also show hypersensitivity to restriction endonucleases when applied by cell poration techniques. These data are reviewed, and new data are presented for Pvu II treatment of the radiosensitive dsb repair-proficient Chinese hamster VC4 mutant, which has been reported to have normal cellular and chromosomal sensitivity to restriction endonucleases and neutrons. We find that VC4 is hypersensitive to blunt-ended dsb generated by PvuII. We conclude that the enhanced sensitivity of this and other repair-proficient mutants to radiation and restriction endonucleases results from a dsb processing defect leading to abnormal conversion of dsb into chromosomal aberrations.