Qualitative differences between replicative and repair synthesis of DNA in normal and transformed mouse cells as measured by precursor discrimination.
Inhibitors of DNA polymerase alpha such as aphidicolin (APC) or 1-beta-D-arabinofuranosyl-cytosine (araC) cause DNA-strand breaks to accumulate after UV-irradiation, at sites where repair resynthesis is inhibited. Transformed cells accumulate fewer such breaks than normal cells do; this may be due to differences in the extent, or the nature, of excision-repair synthesis in transformed and in normal cells. We have looked for differences in the nature of repair synthesis, comparing the labelling of DNA by deoxycytidine (dC) and araC through UV-induced repair in normal and transformed mouse cells. We have made parallel determinations of precursor discrimination in replicative synthesis, and find that normal cells discriminate better against araC in replicative synthesis than do transformed cells. But repair synthesis discriminates against araC less than normal replicative synthesis does, to a similar extent in both cell types. Thus, there are qualitative differences between the DNA polymerases engaged in UV excision repair and replication in normal and transformed mouse cells; but there is no evidence for a predominantly araC-insensitive repair synthesis in transformed cells, such as might account for the difference in break accumulation.
D000818:Animals; D016590:Aphidicolin; D001973:Bromodeoxyuridine / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002869:Chromosome Aberrations; D003561:Cytarabine / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D003841:Deoxycytidine / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology; D004622:Embryo, Mammalian; D051379:Mice; D013379:Substrate Specificity; D014466:Ultraviolet Rays
D004224:Diterpenes; D003561:Cytarabine; D003841:Deoxycytidine; D016590:Aphidicolin; D004247:DNA; D004257:DNA Polymerase II; D001973:Bromodeoxyuridine