Inhibition of polymerases-alpha and -beta completely blocks DNA repair induced by UV irradiation in cultured mouse neuronal cells.
The effects of hydroxyurea, aphidicolin and dideoxythymidine on UV-induced DNA repair of mouse neuronal granular cells were studied. Aphidicolin, which is considered a specific inhibitor of polymerase-alpha, decreased spontaneous DNA synthesis by 93% and totally suppressed DNA repair. Dideoxythymidine, an inhibitor of polymerase-beta, was more potent in decreasing scheduled DNA synthesis than aphidicolin, and also completely blocked the UV-induced DNA repair. Hydroxyurea, a specific inhibitor of ribonucleotide reductase, inhibited scheduled DNA synthesis, but unscheduled DNA synthesis after UV irradiation was always well detectable. Our data suggest that in neuronal cells from 5 to 10 days old mice both polymerases-alpha and -beta are required for both DNA synthesis and repair. These two enzymes may act jointly in filling up the gaps along the DNA molecule and elongating the DNA chain.
D000818:Animals; D016590:Aphidicolin; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors / Q000502:physiology*; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors / Q000502:physiology*; D004260:DNA Repair / Q000187:drug effects*; D015224:Dideoxynucleosides; D004224:Diterpenes / Q000494:pharmacology; D006918:Hydroxyurea / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D013936:Thymidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014466:Ultraviolet Rays
D015224:Dideoxynucleosides; D004224:Diterpenes; C019336:2',3'-dideoxythymidine; D016590:Aphidicolin; D004247:DNA; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D013936:Thymidine; D006918:Hydroxyurea