1. The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination
- Author
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Libri, Alice, Marton, Timea, Deriano, Ludovic, Intégrité du génome, immunité et cancer - Genome integrity, Immunity and Cancer, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and The Deriano laboratory is funded by Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (INSERM), Wordwide Cancer Research (grant # 19–0333), Ligue Nationale Contre le Cancer (Equipe labellis ée 2019) and Institut National du Cancer (INCa, grant # PLBIO19-122). AL received funding from Université de Paris, Sorbonne Paris Cité.
- Subjects
DNA end resection ,[SDV]Life Sciences [q-bio] ,fungi ,DNA double-strand break repair pathway choice ,Review ,QH426-470 ,V(D)J recombination ,non-homologous end-joining ,enzymes and coenzymes (carbohydrates) ,homology-directed repair ,DNA double-strand break ,Genetics ,Molecular Medicine ,Genetics (clinical) - Abstract
International audience; DNA double-strand breaks (DSBs) are highly toxic lesions that can be mended via several DNA repair pathways. Multiple factors can influence the choice and the restrictiveness of repair towards a given pathway in order to warrant the maintenance of genome integrity. During V(D)J recombination, RAG-induced DSBs are (almost) exclusively repaired by the non-homologous end-joining (NHEJ) pathway for the benefit of antigen receptor gene diversity. Here, we review the various parameters that constrain repair of RAG-generated DSBs to NHEJ, including the peculiarity of DNA DSB ends generated by the RAG nuclease, the establishment and maintenance of a post-cleavage synaptic complex, and the protection of DNA ends against resection and (micro)homology-directed repair. In this physiological context, we highlight that certain DSBs have limited DNA repair pathway choice options.
- Published
- 2022
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