Aphidicolin and 1-β-D-arabinofuranosylcytosine strongly inhibit transcriptionally active DNA repair in normal human fibroblasts

Both aphidicolin and 1-β-D-arabinofuranosylcytosine (araC) inactivate DNA polymerases α, δ and e, and accordingly block long-patch excision repair in mammalian cells. We report here that in normal human fibroblasts both compounds strongly inhibit the repair of damage induced by UV or 4-nitroquinoline-1-oxide in the transcriptionally active c-myc gene, as indicated by the appearance of DNA strand breaks in carcinogen-treated cultures that were subsequently incubated in the presence of either polymerase inhibitor. We further demonstrate that the repair of UV photoproducts in the c-myc gene can be monitored by photolysis (313 nm) of DNA repaired in the presence of bromodeoxyuridine (BrdUrd)