DNA polymerase delta mediates excision repair in growing cells damaged with ultraviolet radiation.
In confluent, stationary phase cells, an aphidicolin-sensitive DNA polymerase mediates UV-induced excision repair, but the situation in growing cells is still controversial. The sensitivity of repair synthesis to aphidicolin, an inhibitor of DNA polymerases alpha and delta, was determined in growth phase and confluent normal human fibroblasts (AG1518) using several techniques. Repair synthesis in confluent cells was always inhibited by aphidicolin, no matter which measurement technique was used. However, the inhibition of repair synthesis in growth-phase cells by aphidicolin was only detectable when techniques unaffected by changes in nucleotide metabolism were used. We conclude that UV-induced repair synthesis in growing cells is actually aphidicolin sensitive, but that this inhibition can be obscured by changes in nucleotide metabolism. Employing butylphenyl-deoxyguanosine triphosphate, a potent inhibitor of polymerase alpha and a weak inhibitor of delta, we have obtained evidence that polymerase delta is responsible for repair synthesis in growth-phase cells following UV irradiation.
Hunting
D J
DJ
Department of Nuclear Medicine and Radiobiology, University of Sherbrooke, Quebec, Canada.
Gowans
B J
BJ
Dresler
S L
SL
D016590:Aphidicolin; D001345:Autoradiography; D002455:Cell Division; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis*; D004249:DNA Damage; D004257:DNA Polymerase II / Q000187:drug effects / Q000378:metabolism; D004258:DNA Polymerase III; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology*; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects / Q000378:metabolism*; D003848:Deoxyguanine Nucleotides / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D005347:Fibroblasts; D006801:Humans; D009711:Nucleotides / Q000378:metabolism*; D014466:Ultraviolet Rays
D003848:Deoxyguanine Nucleotides; D004224:Diterpenes; D009711:Nucleotides; D016590:Aphidicolin; C040364:N(2)-(4-n-butylphenyl)-2'-deoxyguanosine 5'-triphosphate; D004247:DNA; D004257:DNA Polymerase II; D004258:DNA Polymerase III; D004259:DNA-Directed DNA Polymerase