FOS IS AN ESSENTIAL COMPONENT OF THE MAMMALIAN UV RESPONSE

Mouse 3T3 fibroblasts lacking c-fos were employed to demonstrate an es sential function of the UV-inducible transcription factor AP-1 (Fos/Ju n) in the response to the cytotoxic effects of short-wavelength ultrav iolet (UVC) radiation. Clonogenic survival and proliferation of cells lacking c-fos were drastically reduced following UV irradiation, This UV hypersensitivity manifests itself primarily in increased cell death , partly by apoptosis, and prolonged recovery time from UV-induced cel l cycle arrest; Go-culture with wild-type cells did not ameliorate the hypersensitivity of mutant cells, Transcriptional induction of the c- Fos target genes collagenase I, stromelysin-l and stromelysin-2 by UV is almost absent in cells lacking c-fos which correlates with a reduce d UV induction of AP-1 DNA-binding and transactivation activity, The r epair of UV-induced DNA lesions was not affected, as shown by unschedu led DNA synthesis and host cell reactivation assays. These data demons trate that c-Fos is involved in a novel protective function other than DNA repair against the harmful consequences of UVC.