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

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...

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Autores principales: Han, Li, Yu, Kefei
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585838/
https://www.ncbi.nlm.nih.gov/pubmed/19001141
http://dx.doi.org/10.1084/jem.20081623
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author Han, Li
Yu, Kefei
author_facet Han, Li
Yu, Kefei
author_sort Han, Li
collection PubMed
description 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.
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spelling pubmed-25858382009-05-24 Altered kinetics of nonhomologous end joining and class switch recombination in ligase IV–deficient B cells Han, Li Yu, Kefei J Exp Med Brief Definitive Reports 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. The Rockefeller University Press 2008-11-24 /pmc/articles/PMC2585838/ /pubmed/19001141 http://dx.doi.org/10.1084/jem.20081623 Text en © 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/).
spellingShingle Brief Definitive Reports
Han, Li
Yu, Kefei
Altered kinetics of nonhomologous end joining and class switch recombination in ligase IV–deficient B cells
title Altered kinetics of nonhomologous end joining and class switch recombination in ligase IV–deficient B cells
title_full Altered kinetics of nonhomologous end joining and class switch recombination in ligase IV–deficient B cells
title_fullStr Altered kinetics of nonhomologous end joining and class switch recombination in ligase IV–deficient B cells
title_full_unstemmed Altered kinetics of nonhomologous end joining and class switch recombination in ligase IV–deficient B cells
title_short Altered kinetics of nonhomologous end joining and class switch recombination in ligase IV–deficient B cells
title_sort altered kinetics of nonhomologous end joining and class switch recombination in ligase iv–deficient b cells
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585838/
https://www.ncbi.nlm.nih.gov/pubmed/19001141
http://dx.doi.org/10.1084/jem.20081623
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