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 massive transcriptional activation of several genes and with the stabilization of the p53 protein. While U.V.-induced transcription of several immediate-response genes depends on U.V.-induced activation of signal transduction generated by non-nuclear mechanisms, stabilization of p53 and the transcription of several delayed-response genes are triggered by U.V.-induced DNA damage. By comparing dose responses for the activation by U.V. of delayed-responsive genes (collagenase 1, metallothionein IIA) in cells from patients with different DNA repair deficiencies (complementation groups of Xeroderma pigmentosum, Cockayne's syndrome and Trichothiodystrophy), we show here that U.V.-induced transcription of these genes does depend on pyrimidine dimers in transcribed regions of the genome (but not on damage in its silent part). Since all cells with defects in DNA repair that had been tested and which lack different 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.
Blattner
C
C
Forschungszentrum Karlsruhe, Institut für Genetik, Karlsruhe, Germany.
Bender
K
K
Herrlich
P
P
Rahmsdorf
H J
HJ
D002460:Cell Line; D017364:Collagenases / Q000235:genetics*; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D016158:Genes, p53; D006801:Humans; D008668:Metallothionein / Q000235:genetics*; D010777:Photochemistry; D011740:Pyrimidine Dimers; D012333:RNA, Messenger; D015398:Signal Transduction; D015533:Transcriptional Activation / Q000528:radiation effects; D014466:Ultraviolet Rays
D011740:Pyrimidine Dimers; D012333:RNA, Messenger; D004247:DNA; D008668:Metallothionein; D017364:Collagenases