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The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination
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-in...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785701/ https://www.ncbi.nlm.nih.gov/pubmed/35082840 http://dx.doi.org/10.3389/fgene.2021.823943 |
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author | Libri, Alice Marton, Timea Deriano, Ludovic |
author_facet | Libri, Alice Marton, Timea Deriano, Ludovic |
author_sort | Libri, Alice |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8785701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87857012022-01-25 The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination Libri, Alice Marton, Timea Deriano, Ludovic Front Genet Genetics 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. Frontiers Media S.A. 2022-01-05 /pmc/articles/PMC8785701/ /pubmed/35082840 http://dx.doi.org/10.3389/fgene.2021.823943 Text en Copyright © 2022 Libri, Marton and Deriano. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Libri, Alice Marton, Timea Deriano, Ludovic The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination |
title | The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination |
title_full | The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination |
title_fullStr | The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination |
title_full_unstemmed | The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination |
title_short | The (Lack of) DNA Double-Strand Break Repair Pathway Choice During V(D)J Recombination |
title_sort | (lack of) dna double-strand break repair pathway choice during v(d)j recombination |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785701/ https://www.ncbi.nlm.nih.gov/pubmed/35082840 http://dx.doi.org/10.3389/fgene.2021.823943 |
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