Skip Navigation



Nucleic Acids Research Advance Access published online on April 24, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn184
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (577K) Freely available
Right arrow Screen PDF (240K) Freely available
Right arrowOA All Versions of this Article:
36/10/3297    most recent
gkn184v1
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 Liang, L.
Right arrow Articles by Tischfield, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liang, L.
Right arrow Articles by Tischfield, J. A.
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

Human DNA ligases I and III, but not ligase IV, are required for microhomology-mediated end joining of DNA double-strand breaks

Li Liang*, Li Deng, Son C. Nguyen, Xin Zhao, Christopher D. Maulion, Changshun Shao and Jay A. Tischfield

Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA

*To whom correspondence should be addressed. Tel: +732 445 5406; Fax: +732 445 1147; Email: liang{at}biology.rutgers.edu

Received January 7, 2008. Revised March 24, 2008. Accepted March 31, 2008.

DNA nonhomologous end-joining (NHEJ) and homologous recombination are two distinct pathways of DNA double-strand break repair in mammalian cells. Biochemical and genetic studies showed that DNA ends can also be joined via microhomology-mediated end joining (MHEJ), especially when proteins responsible for NHEJ, such as Ku, are reduced or absent. While it has been known that Ku-dependent NHEJ requires DNA ligase IV, it is unclear which DNA ligase(s) is required for Ku-independent MHEJ. In this study, we used a cell-free assay to determine the roles of DNA ligases I, III and IV in MHEJ and NHEJ. We found that siRNA mediated down-regulation of DNA ligase I or ligase III in human HTD114 cells led to impaired end joining that was mediated by 2-, 3- or 10-bp microhomology. In addition, nuclear extract from human fibroblasts harboring a mutation in DNA ligase I displayed reduced MHEJ activity. Furthermore, treatment of HTD114 nuclear extracts with an antibody against DNA ligase I or III also significantly reduced MHEJ. These data indicate that DNA ligases I and III are required in MHEJ. DNA ligase IV, on the contrary, is not required in MHEJ but facilitates Ku-dependent NHEJ. Therefore, MHEJ and NHEJ require different DNA ligases.


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
 GeneticsHome page
A. Bozas, K. J. Beumer, J. K. Trautman, and D. Carroll
Genetic Analysis of Zinc-Finger Nuclease-Induced Gene Targeting in Drosophila
Genetics, July 1, 2009; 182(3): 641 - 651.
[Abstract] [Full Text] [PDF]

Home page
 Phil Trans R Soc BHome page
A. Kotnis, L. Du, C. Liu, S. W Popov, and Q. Pan-Hammarstrom
Non-homologous end joining in class switch recombination: the beginning of the end
Phil Trans R Soc B, March 12, 2009; 364(1517): 653 - 665.
[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.