| Autor: |
Ochodnicka‐Mackovicova, Katarina, Mokry, Michal, Haagmans, Martin, Bradley, Ted E., van Noesel, Carel J.M., Guikema, Jeroen E.J. |
| Předmět: |
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| Zdroj: |
European Journal of Immunology; Oct2024, Vol. 54 Issue 10, p1-13, 13p |
| Abstrakt: |
In developing B cells, V(D)J gene recombination is initiated by the RAG1/2 endonuclease complex, introducing double‐stranded DNA breaks (DSBs) in V, D, and J genes and resulting in the formation of the hypervariable parts of immunoglobulins (Ig). Persistent or aberrant RAG1/2 targeting is a potential threat to genome integrity. While RAG1 and RAG2 have been shown to bind various regions genome‐wide, the in vivo off‐target DNA damage instigated by RAG1/2 endonuclease remains less well understood. In the current study, we identified regions containing RAG1/2‐induced DNA breaks in mouse pre‐B cells on a genome‐wide scale using a global DNA DSB detection strategy. We detected 1489 putative RAG1/2‐dependent DSBs, most of which were located outside the Ig loci. DNA sequence motif analysis showed a specific enrichment of RAG1/2‐induced DNA DSBs at GA‐ and CA‐repeats and GC‐rich motifs. These findings provide further insights into RAG1/2 off‐target activity. The ability of RAG1/2 to introduce DSBs on the non‐Ig loci during the endogenous V(D)J recombination emphasizes its genotoxic potential in developing lymphocytes. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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