PHOTOPRODUCTS IN TRANSCRIPTIONALLY ACTIVE DNA INDUCE SIGNAL-TRANSDUCTION TO THE DELAYED U.V.-RESPONSIVE GENES FOR COLLAGENASE AND METALLOTHIONEIN

Mammalian cells in culture react to ultraviolet irradiation with the m assive transcriptional activation of several genes and with the stabil ization of the p53 protein. While U.V.-induced transcription of severa l immediate-response genes depends on U.V.-induced activation of signa l transduction generated by non-nuclear mechanisms, stabilization of p 53 and the transcription of several delayed-response genes are trigger ed by U.V.-induced DNA damage. By comparing dose responses for the act ivation by U.V. of delayed-responsive genes (collagenase 1, metallothi onein IIA) in cells from patients with different DNA repair deficienci es (complementation groups of Xeroderma pigmentosum, Cockayne's syndro me and Trichothiodystrophy), we show here that U.V.-induced transcript ion of these genes does depend on pyrimidine dimers in transcribed reg ions of the genome (but not on damage in its silent part). Since all c ells with defects in DNA repair that had been tested and which lack di fferent enzymes, respond to U.V. with expression of these same genes, functional repair does not appear to be required for the induction of expression, and repair intermediates (which would not be identical in cells of different repair deficiency) cannot be responsible for signal generation.