UV-enhanced reactivation of a UV-damaged reporter gene suggests transcription-coupled repair is UV-inducible in human cells

The genetic disorders xeroderma pigmentosum (XP) and Cockayne syndrome (CS) exhibit deficiencies in the repair of UV-induced DNA damage. CS fibroblast s retain proficient nucleotide excision repair (NER) of inactive (or bulk) DNA, but are deficient in the transcription-coupled repair (TCR) of active genes. In contrast, XP complementation group C (XP-C) fibroblasts retain pr oficient TCR, but are deficient in bulk DNA repair. The remaining NER-defic ient XP groups exhibit deficiencies in both repair pathways. Ad5HCMVsp1lacZ is a recombinant adenovirus vector that is unable to replicate in human fi broblasts, but can efficiently infect and express the P-galactosidase repor ter gene in these cells. We have examined the host cell reactivation (HCR) of beta-galactosidase activity for UV-irradiated Ad5HCMVsp1lacZ in non-irra diated and UV-irradiated normal, XP-B, XP-C, XP-D, XP-F, XP-G, CS-A and CS- B fibroblasts. HCR of P-galactosidase activity for UV-irradiated Ad5HCMVsp1 lacZ was reduced in non-irradiated cells from each of the repair-deficient groups examined (including XP-C) relative to that in non-irradiated normal cells. Prior irradiation of cells with low UV fluences resulted in an enhan cement of HCR for normal and XP-C strains, but not for the remaining XP and CS strains. HCR of the UV-damaged reporter gene in UV-irradiated XP and CS strains was similar to measurements of TCR reported previously for these c ells. These results suggest that UV treatment results in an induced repair of W-damaged DNA in the transcribed strand of an active gene in XP-C and no rmal cells through an enhancement of TCR or a mechanism which involves the TCR pathway.