Abstract
The immune system is the site of intense DNA damage/modification, which occur during the development and maturation of B and T lymphocytes. V(D)J recombination is initiated by the Rag1 and Rag2 proteins and the formation of a DNA double-strand break (DNA dsb). This DNA lesion is repaired through the use of the non-homologous end-joining (NHEJ) pathway, several factors of which have been identified through the survey of immunodeficient conditions in humans and mice. Upon antigenic recognition in secondary lymphoid organs, mature B cells further diversify their repertoire through class switch recombination (CSR). CSR is a region-specific rearrangement process triggered by the activation-induced cytidine deaminase factor and also proceeds through the introduction of DNA dsb. However, unlike V(D)J recombination, CSR does not rely strictly on NHEJ for the repair of the DNA lesion. Instead, CSR, but not V(D)J recombination, requires the major factors of the DNA damage response. V(D)J recombination and CSR thus represent an interesting paradigm to study the regulation among the various DNA repair pathways.
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Acknowledgements
Our work was supported by grants from Institut National de la Santé et de la Recherche Médicale (INSERM), the Agence Nationale de la Recherche (ANR), the Ligue Nationale contre le Cancer (Equipe labellisée LA LIGUE 2005), The Commissariat à l'Energie Atomique (LRC-CEA No40V) and the INCa/Cancéroplole IdF. PR is a scientist from CNRS.
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Soulas-Sprauel, P., Rivera-Munoz, P., Malivert, L. et al. V(D)J and immunoglobulin class switch recombinations: a paradigm to study the regulation of DNA end-joining. Oncogene 26, 7780–7791 (2007). https://doi.org/10.1038/sj.onc.1210875
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DOI: https://doi.org/10.1038/sj.onc.1210875
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