Skip Navigation



Nucleic Acids Research Advance Access published online on March 10, 2008

Nucleic Acids Research, doi:10.1093/nar/gkn094
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (181K) Freely available
Right arrow Screen PDF (190K) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
36/8/2561    most recent
gkn094v1
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 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 Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Schulte-Uentrop, L.
Right arrow Articles by Dahm-Daphi, J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schulte-Uentrop, L.
Right arrow Articles by Dahm-Daphi, J.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Molecular Biology

Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease- and ionizing radiation-induced DNA double-strand breaks

Leonie Schulte-Uentrop1, Raafat A. El-Awady1,2, Lena Schliecker1, Henning Willers3 and Jochen Dahm-Daphi1,*

1Laboratory of Radiobiology & Experimental Radiation Oncology, Department of Radiotherapy and Radiation Oncology, University Medical School Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany 2Department of Tumor Biology, National Cancer Institute, University of Cairo, Egypt and 3Laboratory of Cellular & Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA

*To whom correspondence should be addressed. Tel: +49 40 42803 3930; Fax: +49 40 42803 5139; Email: dahm{at}uke.uni-hamburg.de

Received January 31, 2008. Revised February 15, 2008.

Non-homologous end-joining (NHEJ) of DNA double-strand breaks (DSBs) is mediated by two protein complexes comprising Ku80/Ku70/DNA-PKcs/Artemis and XRCC4/LigaseIV/XLF. Loss of Ku or XRCC4/LigaseIV function compromises the rejoining of radiation-induced DSBs and leads to defective V(D)J recombination. In this study, we sought to define how XRCC4 and Ku80 affect NHEJ of site-directed chromosomal DSBs in murine fibroblasts. We employed a recently developed reporter system based on the rejoining of I-SceI endonuclease-induced DSBs. We found that the frequency of NHEJ was reduced by more than 20-fold in XRCC4–/– compared to XRCC4+/+ cells, while a Ku80 knock-out reduced the rejoining efficiency by only 1.4-fold. In contrast, lack of either XRCC4 or Ku80 increased end degradation and shifted repair towards a mode that used longer terminal microhomologies for rejoining. However, both proteins proved to be essential for the repair of radiation-induced DSBs. The remarkably different phenotype of XRCC4- and Ku80-deficient cells with regard to the repair of enzyme-induced DSBs mirrors the embryonic lethality of XRCC4 knock-out mice as opposed to the viability of the Ku80 knock-out. Thus, I-SceI-induced breaks may resemble DSBs arising during normal DNA metabolism and mouse development. The removal of these breaks likely has different genetic requirements than the repair of radiation-induced DSBs.


The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.


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




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.