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© Deriano Lab / Institut Pasteur
Chromosomes métaphasiques d’une cellule lymphoïde cancéreuse présentant une amplification des gènes Igh et c-myc
Publication : Frontiers in Genetics

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Frontiers in Genetics - 05 Jan 2022

Alice Libri, Timea Marton and Ludovic Deriano

Link to DOI – https://doi.org/10.3389/fgene.2021.823943

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.

Figure. Major parameters restricting DNA repair pathway choice to NHEJ during V(D)J recombination.

https://www.frontiersin.org/articles/10.3389/fgene.2021.823943/full