PREFERENTIAL REPAIR OF UV DAMAGE IN HIGHLY TRANSCRIBED DNA DIMINISHESUV-INDUCED INTRACHROMOSOMAL RECOMBINATION IN MAMMALIAN-CELLS

The relationships among transcription, recombination, DNA damage, and repair in mammalian cells were investigated. We monitored the effects of transcription on UV-induced intrachromosomal recombination between neomycin repeats including a promoterless allele and an inducible hete roallele regulated by the mouse mammary tumor virus promoter. Although transcription and UV light separately stimulated recombination, incre asing transcription levels reduced UV-induced recombination. Preferent ial repair of UV damage in transcribed strands was shown in highly tra nscribed DNA, suggesting that recombination is stimulated by unrepaire d UV damage and that increased DNA repair in highly transcribed allele s removes recombinogenic lesions. This study indicates that the geneti c consequences of DNA damage depend on transcriptional states and prov ides a basis for understanding tissue- and gene-specific responses to DNA-damaging agents.