Evidence for two independent pathways of biologically effective excision repair from its rate and extent in cells cultured from sun-sensitive humans.

Repair-proficient human cells can be sensitized to exposure to UV radiation at 254 nm by postirradiation incubation in the presence of the eukaryotic alpha polymerase inhibitor, aphidicolin. The degree of sensitization has been examined in cells cultured from humans suffering from various types of sun-sensitive syndromes. Xeroderma pigmentosum (XP) variant and Bloom's cell lines (both excision proficient) were strongly sensitized by aphidicolin. An excision repair proficient Cockayne's cell line and a deficient XPD line were both sensitized to a level similar to the sensitivity of excision deficient XPA cells. In contrast, three XPC cell lines which show intermediate UV-induced repair replication and UV sensitivity were sensitized little (in one case) or not at all (in two cases) to UV by postirradiation inhibition of the alpha polymerase. These results lead us to conclude that there are two independent pathways of biologically effective excision repair, the major one of which involves the alpha polymerase and a second, less efficient and slower pathway which is independent of the alpha polymerase and which is the only pathway operating in two of the three XPC strains tested. The rates of biologically effective excision repair were similar in normal, XP variant, and Cockayne's cell lines, but these rates were considerably higher than published rates of dimer excision measured under similar conditions.