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Nucleic Acids Research 2005 33(9):3002-3010; doi:10.1093/nar/gki613
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Published online 24 May 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

Article

DNA damage response and Ku80 function in the vertebrate embryo

Catherine L. Bladen1, Wai K. Lam1, William S. Dynan1 and David J. Kozlowski1,2,*

1Institute of Molecular Medicine and Genetics, Medical College of Georgia Augusta, GA 30912, USA 2Department of Cellular Biology and Anatomy, Medical College of Georgia Augusta, GA 30912, USA

*To whom correspondence should be addressed. Tel: +1 706 721 8760; Fax: +1 706 721 8752; Email: dkozlowski{at}mcg.edu

Received March 20, 2005. Revised May 4, 2005. Accepted May 4, 2005.

Cellular responses to DNA damage reflect the dynamic integration of cell cycle control, cell–cell interactions and tissue-specific patterns of gene regulation that occurs in vivo but is not recapitulated in cell culture models. Here we describe use of the zebrafish embryo as a model system to identify determinants of the in vivo response to ionizing radiation-induced DNA damage. To demonstrate the utility of the model we cloned and characterized the embryonic function of the XRCC5 gene, which encodes Ku80, an essential component of the nonhomologous end joining pathway of DNA repair. After the onset of zygotic transcription, Ku80 mRNA accumulates in a tissue-specific pattern, which includes proliferative zones of the retina and central nervous system. In the absence of genotoxic stress, zebrafish embryos with reduced Ku80 function develop normally. However, low dose irradiation of these embryos during gastrulation leads to marked apoptosis throughout the developing central nervous system. Apoptosis is p53 dependent, indicating that it is a downstream consequence of unrepaired DNA damage. Results suggest that nonhomologous end joining components mediate DNA repair to promote survival of irradiated cells during embryogenesis.

DDBJ/EMBL/GenBank accession no AY877316


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