Novobiocin does not inhibit DNA repair in an active gene.

Novobiocin, an inhibitor of type II topoisomerase, has been reported to inhibit u.v.-induced DNA repair in a number of established mammalian cell lines; we have confirmed this general observation in primary cultures of human epidermal keratinocytes. Using a recently developed technique for measuring pyrimidine dimer frequencies in genomic restriction fragments, we have determined the extent of DNA repair in the active, essential dihydrofolate reductase (DHFR) gene. Novobiocin did not affect repair of the DHFR gene in keratinocytes or in a Chinese hamster ovary (CHO) cell line over a 24-h period following irradiation with 20 J/m2 u.v. These findings suggest that qualitative differences exist in the repair pathways in different genomic regions; topoisomerase II may not have an essential role in repair of active genes but may be required for repair of other regions in the genome.