c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF.
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.
Christmann
Markus
M
Department of Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany.
Tomicic
Maja T
MT
Origer
Judith
J
Aasland
Dorthe
D
Kaina
Bernd
B
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D053904:DNA Breaks, Single-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D016762:Genes, fos / Q000235:genetics / Q000502:physiology*; D005816:Genetic Complementation Test; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011740:Pyrimidine Dimers / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays; D000099250:DNA Excision Repair Protein ERCC-5
D004247:DNA; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D011740:Pyrimidine Dimers; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C095888:xeroderma pigmentosum group F protein