Skip Navigation


Mutagenesis Advance Access originally published online on March 7, 2007
Mutagenesis 2007 22(3):217-233; doi:10.1093/mutage/gem007
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
22/3/217    most recent
gem007v1
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 (5)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Kuhfittig-Kulle, S.
Right arrow Articles by Pfeiffer, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kuhfittig-Kulle, S.
Right arrow Articles by Pfeiffer, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


© The Author 2007. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

The mutagenic potential of non-homologous end joining in the absence of the NHEJ core factors Ku70/80, DNA-PKcs and XRCC4-LigIV

Steffi Kuhfittig-Kulle1,2, Elke Feldmann1, Andrea Odersky1,3, Aneta Kuliczkowska1,4, Wolfgang Goedecke1, Angelika Eggert2 and Petra Pfeiffer1,5,*

1Department of Biology and Geography, Institute of Genetics, University of Duisburg-Essen, Universitätsstrasse 5, D-45117 Essen, Germany 2Present address: Department of Pediatric Hematology/Oncology, University Children's Hospital of Essen, Hufelandstrasse 55, D-45122 Essen, Germany 3Present address: Institute of Biochemistry and Molecular Biology 2, University of Düsseldorf Medical School, Universitätsstrasse 1, D-40225 Düsseldorf, Germany 4Present address: Dr Fooke Laboratories GmbH, Mainstrasse 85, D-41469 Neuss, Germany 5Present address: Institute for Genetics, University of Cologne, Zülpicherstrasse 47, D-50674 Köln, Germany

Non-homologous end joining (NHEJ), the major pathway of double-strand break (DSB) repair in mammalian cells, comprises two subpathways: one that requires the three core factors Ku70/80, DNA-PKcs and XRCC4/LigIV (DNA-PK-dependent NHEJ) and the other that is independent of these factors. Using a cell-free NHEJ assay, we have investigated the ability of three Chinese hamster ovary (CHO) mutants deficient in Ku80 (xrs6), DNA-PKcs (XR-C1) and XRCC4 (XR-1) in comparison with CHO-K1 wild-type cells to rejoin non-compatible DSB ends. Both NHEJ efficiency and fidelity are strongly reduced in the mutants with xrs6 and XR-1 exhibiting the strongest reduction and XR-C1 displaying a phenotype intermediate between the wild-type and the other two mutants indicating a non-essential but facilitating role of DNA-PKcs in NHEJ. The decrease in fidelity in the mutants is expressed by an increase of deletion junctions formed at microhomologies (µhom) near the DSB (microhomology-mediated non-homologous end joining: µhomNHEJ). Using a novel µhomNHEJ assay, we show that µhom regions of 6–10 bp that are located directly at the DSB termini strongly enhance the mutagenic µhomNHEJ reaction even in the wild type. Due to its error proneness, DNA-PK-independent µhomNHEJ may actively promote genome instability. It will, therefore, be of increasing importance to examine NHEJ fidelity in the context with tumorigenesis and cellular senescence for which we here provide two efficient and reliable tools.

* To whom correspondence should be addressed. Email: petra.pfeiffer{at}uni-koeln.de

Received on November 11, 2006; revised on January 18, 2007; accepted on January 22, 2007.


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
 Nucleic Acids ResHome page
E. M. Taylor, S. M. Cecillon, A. Bonis, J. R. Chapman, L. F. Povirk, and H. D. Lindsay
The Mre11/Rad50/Nbs1 complex functions in resection-based DNA end joining in Xenopus laevis
Nucleic Acids Res., November 5, 2009; (2009) gkp905v1.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. Ahmad, A. R. Robinson, A. Duensing, E. van Drunen, H. B. Beverloo, D. B. Weisberg, P. Hasty, J. H. J. Hoeijmakers, and L. J. Niedernhofer
ERCC1-XPF Endonuclease Facilitates DNA Double-Strand Break Repair
Mol. Cell. Biol., August 15, 2008; 28(16): 5082 - 5092.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
W. Y. Mansour, S. Schumacher, R. Rosskopf, T. Rhein, F. Schmidt-Petersen, F. Gatzemeier, F. Haag, K. Borgmann, H. Willers, and J. Dahm-Daphi
Hierarchy of nonhomologous end-joining, single-strand annealing and gene conversion at site-directed DNA double-strand breaks
Nucleic Acids Res., July 1, 2008; 36(12): 4088 - 4098.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
L. Schulte-Uentrop, R. A. El-Awady, L. Schliecker, H. Willers, and J. Dahm-Daphi
Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease- and ionizing radiation-induced DNA double-strand breaks
Nucleic Acids Res., May 1, 2008; 36(8): 2561 - 2569.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
K. Matsuzaki, A. Shinohara, and M. Shinohara
Forkhead-Associated Domain of Yeast Xrs2, a Homolog of Human Nbs1, Promotes Nonhomologous End Joining Through Interaction With a Ligase IV Partner Protein, Lif1
Genetics, May 1, 2008; 179(1): 213 - 225.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
L. F. Povirk, R.-Z. Zhou, D. A. Ramsden, S. P. Lees-Miller, and K. Valerie
Phosphorylation in the serine/threonine 2609-2647 cluster promotes but is not essential for DNA-dependent protein kinase-mediated nonhomologous end joining in human whole-cell extracts
Nucleic Acids Res., June 9, 2007; 35(12): 3869 - 3878.
[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.