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A correction to this article has been published: Han and Yu, J. Exp. Med. 205 (13) 3215
Published online
doi:10.1084/jem.20081623
The Journal of Experimental Medicine, Vol. 205, No. 12, 2745-2753
The Rockefeller University Press, 0022-1007 $30.00
© Han et al.
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BRIEF DEFINITIVE REPORT

 Altered kinetics of nonhomologous end joining and class switch recombination in ligase IV–deficient B cells

Li Han and Kefei Yu

Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824

CORRESPONDENCE Kefei Yu: yuke{at}msu.edu

Immunoglobulin heavy chain class switch recombination (CSR) is believed to occur through the generation and repair of DNA double-strand breaks (DSBs) in the long and repetitive switch regions. Although implied, the role of the major vertebrate DSB repair pathway, nonhomologous end joining (NHEJ), in CSR has been controversial. By somatic gene targeting of DNA ligase IV (Lig4; a key component of NHEJ) in a B cell line (CH12F3) capable of highly efficient CSR in vitro, we found that NHEJ is required for efficient CSR. Disruption of the Lig4 gene in CH12F3 cells severely inhibits the initial rate of CSR and causes a late cell proliferation defect under cytokine stimulation. However, unlike V(D)J recombination, which absolutely requires NHEJ, CSR accumulates to a substantial level in Lig4-null cells. The data revealed a fast-acting NHEJ and a slow-acting alterative end joining of switch region breaks during CSR.

© 2008 Han and Yu This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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