This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ghosh, R Articles by Cerutti, P Search for Related Content PubMed PubMed Citation Articles by Ghosh, R Articles by Cerutti, P

 Previous Article  |  Next Article 

Mol Cell Biol. 1993 November; 13(11): 6992-6999

UVB-induced DNA breaks interfere with transcriptional induction of c-fos.

Department of Carcinogenesis, Swiss Institute for Experimental Cancer Research, Lausanne.

ABSTRACT

Oxidative stress may play an important role in the carcinogenic action of UVB light (290 to 320 nm). UVB light induces the growth-related immediate-early gene c-fos in JB6 mouse epidermal cells, but at the same time it causes structural damage to DNA, in particular DNA strand breakage. We have studied the effect of the modulation of the frequencies of DNA breaks on the transcriptional induction of c-fos by changing the cellular antioxidant defense or by inhibiting break repair. Reduction of UVB-induced DNA breakage in a stable transfectant with an increased complement of glutathione peroxidase enhanced the induction of c-fos. In contrast, c-fos induction was diminished in stable transfectants with Cu,Zn-superoxide dismutase. Increasing the stationary concentration of UVB-induced DNA breaks by inhibition of repair in the presence of the adenosine diphosphoribose (ADPR)-transferase inhibitor 3-amino-benzamide suppressed the induction of c-fos. We conclude that DNA breaks which are induced by UVB via oxidative processes interfere with the transcriptional induction of c-fos. DNA breaks appear to exert a long-range effect on chromatin conformation which is incompatible with efficient transcription. This notion is supported by the observation that inhibition of break rejoining by 3-amino-benzamide suppressed the UVB induction of the endogenous c-fos gene and of a stably integrated construct containing the c-fos regulatory sequences linked to a reporter gene. In contrast, the induction of the same construct was not inhibited when it remained extrachromosomal in transient transfection experiments.

This article has been cited by other articles:

• Bair, W. B. III, Hart, N., Einspahr, J., Liu, G., Dong, Z., Alberts, D., Bowden, G. T. (2002). Inhibitory Effects of Sodium Salicylate and Acetylsalicylic Acid on UVB-induced Mouse Skin Carcinogenesis. Cancer Epidemiol. Biomarkers Prev. 11: 1645-1652 [Abstract] [Full Text]  
• Nomura, M., Kaji, A., He, Z., Ma, W.-Y., Miyamoto, K.-i., Yang, C. S., Dong, Z. (2001). Inhibitory Mechanisms of Tea Polyphenols on the Ultraviolet B-activated Phosphatidylinositol 3-Kinase-dependent Pathway. J. Biol. Chem. 276: 46624-46631 [Abstract] [Full Text]  
• Fritz, G., Kaina, B. (2001). Transcriptional activation of the small GTPase gene rhoB by genotoxic stress is regulated via a CCAAT element. Nucleic Acids Res 29: 792-798 [Abstract] [Full Text]  
• Zhao, H., Jin, S., Fan, F., Fan, W., Tong, T., Zhan, Q. (2000). Activation of the Transcription Factor Oct-1 in Response to DNA Damage. Cancer Res. 60: 6276-6280 [Abstract] [Full Text]  
• Huang, C., Ma, W.-Y., Young, M. R., Colburn, N., Dong, Z. (1998). Shortage of mitogen-activated protein kinase is responsible for resistance to AP-1 transactivation and transformation in mouse JB6 cells. Proc. Natl. Acad. Sci. USA 95: 156-161 [Abstract] [Full Text]  
• Renzing, J, Hansen, S, Lane, D. (1996). Oxidative stress is involved in the UV activation of p53. J. Cell Sci. 109: 1105-1112 [Abstract]  
• Fritz, G., Kaina, B., Aktories, K. (1995). The Ras-related Small GTP-binding Protein RhoB Is Immediate-early Inducible by DNA Damaging Treatments. J. Biol. Chem. 270: 25172-25177 [Abstract] [Full Text]