Aphidicolin-sensitive DNA repair synthesis in human fibroblasts damaged with bleomycin is distinct from UV-induced repair

Abstract

Human fibroblasts repair DNA damaged by bleomycin through both short-patch and long-patch pathways, mediated by an aphidicolin-resistant (β) and aphidicolin-sensitive (δ) DNA polymerase respectively (DiGiuseppe,J.A. and Dresler,S.L. (1989) Biochemistry, 28, 9515–9520). Despite certain similarities, aphidicolin-sensitive repair synthesis induced by bleomycin can be distinguished genetically and biochemically from that elicited by UV radiation. Permeable xeroderma pigmentosum fibroblasts of complementation groups A and G, completely deficient in UV-induced repair, display aphidicolin-sensitive repair synthesis dependent upon dose of bleomycin. Furthermore, the ribonucleotide dependence of long-patch repair induced by bleomycin differs from that of UV repair with respect to substrate specificity and apparent K_m for ATP. This novel ATPase activity mediates a step prior to polymerization. By contrast, short-patch repair synthesis does not require ATP. These data suggest that, in addition to short-patch repair, human cells possess two distinct long-patch excision repair pathways. We propose that these pathways represent strand-break, base and nucleotide excision repair respectively.