ATF3 and p15(PAF) are novel gatekeepers of genomic integrity upon UV stress

Turchi, L., Fareh, M., Aberdam, E., Kitajima, S., Simpson, F, Wicking, C., Aberdam, D. and Virolle, T. (2009) ATF3 and p15(PAF) are novel gatekeepers of genomic integrity upon UV stress. Cell Death and Differentiation, 16 5: 728-737. doi:10.1038/cdd.2009.2

Author Turchi, L.
Fareh, M.
Aberdam, E.
Kitajima, S.
Simpson, F
Wicking, C.
Aberdam, D.
Virolle, T.
Title ATF3 and p15(PAF) are novel gatekeepers of genomic integrity upon UV stress
Formatted title
ATF3 and p15PAF are novel gatekeepers of genomic integrity upon UV stress 
Journal name Cell Death and Differentiation   Check publisher's open access policy
ISSN 1350-9047
Publication date 2009-05
Sub-type Article (original research)
DOI 10.1038/cdd.2009.2
Volume 16
Issue 5
Start page 728
End page 737
Total pages 10
Editor Gerry Melino
Place of publication London, Hamps, U.K.
Publisher Nature Publishing Group
Collection year 2010
Language eng
Subject 1004 Medical Biotechnology
970106 Expanding Knowledge in the Biological Sciences
060199 Biochemistry and Cell Biology not elsewhere classified
Formatted abstract
After genotoxic stress, normal cells trigger DNA repair or, if unable to repair, undergo apoptosis to eradicate the cells that bear the risk of becoming tumorigenic. Here we show that repression of the transcription factor, activating transcription factor 3 (ATF3), after ultraviolet (UV)-mediated genotoxic stress impairs the DNA repair process. We provide evidence that ATF3 directly regulates the proliferating cell nuclear antigen (PCNA)-associated factor KIAA0101/p15PAF. We further show that the expressions of ATF3 and p15PAF is sufficient to trigger the DNA repair machinery, and that attenuation of their expression alters DNA repair mechanisms. We show that the expression of p15PAF compensates for a lack of ATF3 expression, thereby constituting a major effector of ATF3 in the DNA repair process. In addition, we provide evidence that p15PAF expression is required for the correct function of PCNA during DNA repair, as prevention of their interaction significantly alters DNA repair mechanisms. Finally, defective DNA repair, because of the downregulation of p15PAF expression, rendered the cells more sensitive to UV-induced cell death. Therefore, our results suggest ATF3 and p15PAF as novel gatekeepers of genomic integrity after UV exposure.
Keyword DNA repair
Activating transcription factor-3
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
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Citation counts: TR Web of Science Citation Count  Cited 38 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 03 Sep 2009, 08:18:54 EST by Mr Andrew Martlew on behalf of Institute for Molecular Bioscience