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PMID: 17606631 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Role for DNA repair factor XRCC4 in immunoglobulin class switch recombination.

The Journal of experimental medicine ·Vol. 204 ·No. 7 ·2007-07-09 ·Pages 1717-27

Soulas-Sprauel P, Le Guyader G, Rivera-Munoz P, Abramowski V, Olivier-Martin C, Goujet-Zalc C, Charneau P, de Villartay JP

Abstract

V(D)J recombination and immunoglobulin class switch recombination (CSR) are two somatic rearrangement mechanisms that proceed through the introduction of double-strand breaks (DSBs) in DNA. Although the DNA repair factor XRCC4 is essential for the resolution of DNA DSB during V(D)J recombination, its role in CSR has not been established. To bypass the embryonic lethality of XRCC4 deletion in mice, we developed a conditional XRCC4 knockout (KO) using LoxP-flanked XRCC4 cDNA lentiviral transgenesis. B lymphocyte restricted deletion of XRCC4 in these mice lead to an average two-fold reduction in CSR in vivo and in vitro. Our results connect XRCC4 and the nonhomologous end joining DNA repair pathway to CSR while reflecting the possible use of an alternative pathway in the repair of CSR DSB in the absence of XRCC4. In addition, this new conditional KO approach should be useful in studying other lethal mutations in mice.

MeSH Terms
Animals B-Lymphocytes/immunology DNA Repair DNA-Binding Proteins/deficiency,genetics Genes, Lethal Immunoglobulin Class Switching Lentivirus/genetics Mice Mice, Knockout Mice, Transgenic Mutation
Chemicals
DNA-Binding Proteins XRCC4 protein, human XRCC4 protein, mouse
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Soulas-Sprauel Pauline
Institut National de la Santé et de la Recherche Médicale Unité 768, F-75015 Paris, France.
Le Guyader Gwenaël
Rivera-Munoz Paola
Abramowski Vincent
Olivier-Martin Christelle
Goujet-Zalc Cécile
Charneau Pierre
de Villartay Jean-Pierre
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20070255
Published
2007-07-09
Epub
2007-00-02
Pages
1717-27
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118634
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20070255 PMC Full Text View journal details
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