The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination

被引：12
作者：
Libri, Alice [1 ]
Marton, Timea [1 ]
Deriano, Ludovic [1 ]
机构：
[1] Univ Paris, Inst Pasteur, Equipe Labellisee Ligue Le Canc, INSERM,Genome Integr Immun & Canc Unit,U1223, Paris, France
来源：
FRONTIERS IN GENETICS | 2022年 / 12卷
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; DEPENDENT PROTEIN-KINASE; XRCC4-DNA LIGASE-IV; END-JOINING FACTOR; DAMAGE RESPONSE; CHROMOSOMAL TRANSLOCATIONS; FUNCTIONAL REDUNDANCY; GENE AMPLIFICATION; CRYSTAL-STRUCTURE; RAG PROTEINS; LONG-RANGE;
D O I：
10.3389/fgene.2021.823943
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
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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页数：10
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