Nucleic Acids Research Advance Access originally published online on November 27, 2006
Nucleic Acids Research 2006 34(22):6530-6539; doi:10.1093/nar/gkl895
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Nucleic Acids Research, 2006, Vol. 34, No. 22 6530-6539
© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF
Department of Toxicology, University of Mainz Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany
*To whom correspondence should be addressed. Tel: +49 6131 393 3246; Fax: +49 6131 230506; Email: kaina{at}uni-mainz.de
Received June 1, 2006. Revised October 10, 2006. Accepted October 10, 2006.
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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