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

First Author  Soulas-Sprauel P Year  2007
Journal  J Exp Med Volume  204
Issue  7 Pages  1717-27
PubMed ID  17606631 Mgi Jnum  J:125880
Mgi Id  MGI:3760068 Doi  10.1084/jem.20070255
Citation  Soulas-Sprauel P, et al. (2007) Role for DNA repair factor XRCC4 in immunoglobulin class switch recombination. J Exp Med 204(7):1717-27
abstractText  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.
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