High-complexity of DNA double-strand breaks is key for alternative end-joining choice.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
03 Aug 2024
03 Aug 2024
Historique:
received:
30
01
2024
accepted:
26
07
2024
medline:
3
8
2024
pubmed:
3
8
2024
entrez:
2
8
2024
Statut:
epublish
Résumé
The repair of DNA double-strand breaks (DSBs) through alternative non-homologous end-joining (alt-NHEJ) pathway significantly contributes to genetic instability. However, the mechanism governing alt-NHEJ pathway choice, particularly its association with DSB complexity, remains elusive due to the absence of a suitable reporter system. In this study, we established a unique Escherichia coli reporter system for detecting complex DSB-initiated alternative end-joining (A-EJ), an alt-NHEJ-like pathway. By utilizing various types of ionizing radiation to generate DSBs with varying degrees of complexity, we discovered that high complexity of DSBs might be a determinant for A-EJ choice. To facilitate efficient repair of high-complexity DSBs, A-EJ employs distinct molecular patterns such as longer micro-homologous junctions and non-templated nucleotide addition. Furthermore, the A-EJ choice is modulated by the degree of homology near DSB loci, competing with homologous recombination machinery. These findings further enhance the understanding of A-EJ/alt-NHEJ pathway choice.
Identifiants
pubmed: 39095441
doi: 10.1038/s42003-024-06640-5
pii: 10.1038/s42003-024-06640-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
936Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 12135016
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 12075275
Informations de copyright
© 2024. The Author(s).
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