DNA Repair in Radiation Sensitive Mutants of Mammalian Cells: Possible Involvement of DNA Topoisomerases

Abstract

Mutants are invaluable in the study of DNA repair processes. The past 10 years have seen a rapid proliferation of papers describing the isolation of mammalian cell mutants exhibiting DNA repair abnormalities. A variety of DNA-damaging agents, including radiation, alkylating agents and bleomycin, have been used to select mutants. This mini-review will concentrate on radiation (particularly ionizing radiation)-sensitive mutants, whether selected directly on the basis of radiation sensitivity or subsequently found to be cross-sensitive to radiation. Commonly observed DNA repair defects are associated with sensitivity to radiation. For UV-sensitive mutants a defect in the incision step of excision repair is frequently seen. For ionizing radiation-sensitive mutants, the common feature is a defect in the repair of DNA strand breaks. This may take the form of a reduced rate of strand-break rejoining or of a lowering in the fidelity of rejoining. Recent work suggests that the DNA topoisomerases may participate in the repair of DNA strand breaks and that strand breaks induced by both topoisomerase inhibitory drugs and radiation may be repaired by common pathways.