期刊
FRONTIERS IN GENETICS
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2021.823943
关键词
DNA double-strand break; V(D)J recombination; non-homologous end-joining; homology-directed repair; DNA end resection; DNA double-strand break repair pathway choice
资金
- Institut Pasteur
- Wordwide Cancer Research [19-0333]
- Ligue Nationale Contre le Cancer (Equipe labellis ee 2019)
- Institut National du Cancer (INCa) [PLBIO19-122]
- Universite de Paris, Sorbonne Paris Cite
- Institut National de la Sante et de la Recherche Medicale (INSERM)
DNA double-strand breaks are highly toxic and can be repaired via multiple DNA repair pathways. During V(D)J recombination, certain parameters restrict the repair of DSBs to the non-homologous end-joining pathway.
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.
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