c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF - DNA

c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF
November 27, 2006
Markus Christmann, Maja T. Tomicic, Judith Origer, Dorthe Aasland and Bernd Kaina*
Department of Toxicology, University of Mainz Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany
Nucleic Acids Research
ABSTRACT
Cells deficient in c-Fos are hypersensitive to ultraviolet (UV-C) light. Here we demonstrate that mouse embryonic fibroblasts lacking c-Fos (fos?/?) are defective in the repair of UV-C induced DNA lesions. They show a decreased rate of sealing of repair-mediated DNA strand breaks and are unable to remove cyclobutane pyrimidine dimers from DNA. A search for genes responsible for the DNA repair defect revealed that upon UV-C treatment the level of xpf and xpg mRNA declined but, in contrast to the wild type (wt), did not recover in fos?/? cells. The observed decline in xpf and xpg mRNA is due to impaired re-synthesis, as shown by experiments using actinomycin D. Block of xpf transcription resulted in a lack of XPF protein after irradiation of fos?/? cells, whereas the XPF level normalized quickly in the wt. Although the xpg mRNA level was reduced, the amount of XPG protein was not altered in c-Fos-deficient cells after UV-C, due to higher stability of the XPG protein. The data suggest a new role for c-Fos in cells exposed to genotoxic stress. Being part of the transcription factor AP-1, c-Fos stimulates NER via the upregulation of xpf and thus plays a central role in the recovery of cells from UV light induced DNA damage.
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