VARIATIONS IN TRANSCRIPTION-REPAIR COUPLING IN MOUSE CELLS

Formation and repair of W-induced cyclobutane pyrimidine dimers (CPDs) was examined in three different genes in mouse L cells: 1) a stably i ntegrated insert (called LTL), consisting of a herpes simplex virus th ymidine kinase gene (th) fused to a hormone inducible promotor (LTR); 2) the constitutively expressed protooncogene c-abl; and 3) the inacti ve immunoglobulin J chain gene, Transcription of the tk gene is induce d >50-fold by dexamethasone. There is a nonuniform distribution of CPD s in LTL DNA irradiated in vitro, being 4-fold higher in the LTR than in the th gene, indicating the LTR may be damaged preferentially in ir radiated cells, Repair of CPDs occurs efficiently in both strands of L TL and is unaffected by hormone induction of th gene transcription. Tr anscription of tit mRNA is very sensitive to UV damage and follows sin gle hit kinetics with UV dose. Furthermore, tit mRNA expression rapidl y recovers during repair incubation, Transcription-coupled repair occu rs in these cells, however, since only the transcribed strand of c-abl is efficiently repaired of CPDs; the nontranscribed strand as well as both strands of the J chain gene are inefficiently repaired. Thus, re pair in the LTL construct may reflect a lack of transcription-coupled repair in either the LTR promotor or the LTL insertion region of chrom atin.