The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination
| Autor: | Libri, Alice, Marton, Timea, Deriano, Ludovic |
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| Přispěvatelé: | 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), 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. |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Frontiers in Genetics, Vol 12 (2022) Frontiers in Genetics Frontiers in Genetics, 2022, 12, pp.823943. ⟨10.3389/fgene.2021.823943⟩ |
| ISSN: | 1664-8021 |
| DOI: | 10.3389/fgene.2021.823943 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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