Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (192K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (25)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Marangoni, E.
Right arrow Articles by Jeggo, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Marangoni, E.
Right arrow Articles by Jeggo, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2000, Vol. 28, No. 23 4778-4782
© 2000 Oxford University Press

A Ku80 fragment with dominant negative activity imparts a radiosensitive phenotype to CHO-K1 cells

Elisabetta Marangoni, Nicolas Foray1, Mark O’Driscoll2, Sétha Douc-Rasy3, Jacques Bernier4, Jean Bourhis* and Penny Jeggo2

Unité Propre de l’Enseignement Supérieur ‘Radiosensibilité-Radiocarcinogenèse Humaine’ (UPRES EA no. 2710, Pr. Eschwege), IFR no. 54, Institut Gustave Roussy, Villejuif, France, 1U 350 INSERM–Institut Curie, Centre Universitaire, 91405 Orsay, France, 2MRC Cell Mutation Unit, University of Sussex, Brighton, UK, 3Unité des Marqueurs Génétiques, Institut Gustave Roussy, Villejuif, France and 4Hôpital Cantonal, Servizio di Radio-oncologia, Bellinzona, Switzerland

DNA non-homologous end joining, the major mechanism for the repair of DNA double-strands breaks (DSB) in mammalian cells requires the DNA-dependent protein kinase (DNA-PK), a complex composed of a large catalytic subunit of 460 kDa (DNA-PKcs) and the heterodimer Ku70–Ku80 that binds to double-stranded DNA ends. Mutations in any of the three subunits of DNA-PK lead to extreme radiosensitivity and DSB repair deficiency. Here we show that the 283 C-terminal amino acids of Ku80 introduced into the Chinese hamster ovary cell line CHO-K1 have a dominant negative effect. Expression of Ku(449–732) in CHO cells was verified by northern blot analysis and resulted in decreased Ku-dependent DNA end-binding activity, a diminished capacity to repair DSBs as determined by pulsed field gel electrophoresis and decreased radioresistance determined by clonogenic survival. The stable modifications observed at the molecular and cellular level suggest that this fragment of Ku80 confers a dominant negative effect providing an important mechanism to sensitise radioresistant cells.

* To whom correspondence should be addressed. Tel: +33 1 42 11 49 98; Fax: +33 1 42 11 52 81; Email: bourhis{at}igr.fr


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Guirouilh-Barbat, E. Rass, I. Plo, P. Bertrand, and B. S. Lopez
Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends
PNAS, December 26, 2007; 104(52): 20902 - 20907.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Geng, K. C. Cuneo, A. Fu, T. Tu, P. W. Atadja, and D. E. Hallahan
Histone Deacetylase (HDAC) Inhibitor LBH589 Increases Duration of {gamma}-H2AX Foci and Confines HDAC4 to the Cytoplasm in Irradiated Non-Small Cell Lung Cancer
Cancer Res., December 1, 2006; 66(23): 11298 - 11304.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Drouet, P. Frit, C. Delteil, J.-P. de Villartay, B. Salles, and P. Calsou
Interplay between Ku, Artemis, and the DNA-dependent Protein Kinase Catalytic Subunit at DNA Ends
J. Biol. Chem., September 22, 2006; 281(38): 27784 - 27793.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Toulany, U. Kasten-Pisula, I. Brammer, S. Wang, J. Chen, K. Dittmann, M. Baumann, E. Dikomey, and H. P. Rodemann
Blockage of Epidermal Growth Factor Receptor-Phosphatidylinositol 3-Kinase-AKT Signaling Increases Radiosensitivity of K-RAS Mutated Human Tumor Cells In vitro by Affecting DNA Repair.
Clin. Cancer Res., July 1, 2006; 12(13): 4119 - 4126.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. Munshi, J. F. Kurland, T. Nishikawa, T. Tanaka, M. L. Hobbs, S. L. Tucker, S. Ismail, C. Stevens, and R. E. Meyn
Histone Deacetylase Inhibitors Radiosensitize Human Melanoma Cells by Suppressing DNA Repair Activity
Clin. Cancer Res., July 1, 2005; 11(13): 4912 - 4922.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. W. Lim, H. Kim, and K. H. Kim
The Ku Antigen-Recombination Signal-binding Protein J{kappa} Complex Binds to the Nuclear Factor-{kappa}B p50 Promoter and Acts as a Positive Regulator of p50 Expression in Human Gastric Cancer Cells
J. Biol. Chem., January 2, 2004; 279(1): 231 - 237.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Y. Song, J. W. Lim, H. Kim, T. Morio, and K. H. Kim
Oxidative Stress Induces Nuclear Loss of DNA Repair Proteins Ku70 and Ku80 and Apoptosis in Pancreatic Acinar AR42J Cells
J. Biol. Chem., September 19, 2003; 278(38): 36676 - 36687.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. W. Lim, H. Kim, and K. H. Kim
Expression of Ku70 and Ku80 Mediated by NF-kappa B and Cyclooxygenase-2 Is Related to Proliferation of Human Gastric Cancer Cells
J. Biol. Chem., November 22, 2002; 277(48): 46093 - 46100.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
C. Vens, E. Dahmen-Mooren, M. Verwijs-Janssen, W. Blyweert, L. Graversen, H. Bartelink, and A. C. Begg
The role of DNA polymerase {beta} in determining sensitivity to ionizing radiation in human tumor cells
Nucleic Acids Res., July 1, 2002; 30(13): 2995 - 3004.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.