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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 r...

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Autores principales: Christmann, Markus, Tomicic, Maja T., Origer, Judith, Aasland, Dorthe, Kaina, Bernd
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1702502/
https://www.ncbi.nlm.nih.gov/pubmed/17130154
http://dx.doi.org/10.1093/nar/gkl895
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author Christmann, Markus
Tomicic, Maja T.
Origer, Judith
Aasland, Dorthe
Kaina, Bernd
author_facet Christmann, Markus
Tomicic, Maja T.
Origer, Judith
Aasland, Dorthe
Kaina, Bernd
author_sort Christmann, Markus
collection PubMed
description 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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spelling pubmed-17025022006-12-26 c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF Christmann, Markus Tomicic, Maja T. Origer, Judith Aasland, Dorthe Kaina, Bernd Nucleic Acids Res Molecular Biology 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. Oxford University Press 2006-12 2006-11-27 /pmc/articles/PMC1702502/ /pubmed/17130154 http://dx.doi.org/10.1093/nar/gkl895 Text en © 2006 The Author(s).
spellingShingle Molecular Biology
Christmann, Markus
Tomicic, Maja T.
Origer, Judith
Aasland, Dorthe
Kaina, Bernd
c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF
title c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF
title_full c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF
title_fullStr c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF
title_full_unstemmed c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF
title_short c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF
title_sort c-fos is required for excision repair of uv-light induced dna lesions by triggering the re-synthesis of xpf
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1702502/
https://www.ncbi.nlm.nih.gov/pubmed/17130154
http://dx.doi.org/10.1093/nar/gkl895
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