Aphidicolin-sensitive DNA repair synthesis in human fibroblasts damaged with bleomycin is distinct from UV-induced repair.
Human fibroblasts repair DNA damaged by bleomycin through both short-patch and long-patch pathways, mediated by an aphidicolin-resistant (beta) and aphidicolin-sensitive (delta) 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 Km 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.
Division of Hematology--Oncology, St Louis Children's Hospital, St Louis, MO 63110.
J A
JA
DiGiuseppe
D J
DJ
Hunting
S L
SL
Dresler
D000255:Adenosine Triphosphate / Q000378:metabolism; D016590:Aphidicolin; D001761:Bleomycin / Q000494:pharmacology*; D002460:Cell Line; D004249:DNA Damage; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D004261:DNA Replication / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008957:Models, Genetic; D014466:Ultraviolet Rays
D004224:Diterpenes; D001761:Bleomycin; D016590:Aphidicolin; D000255:Adenosine Triphosphate; D004257:DNA Polymerase II