{
  "abstract": "V(D)J recombination generates antigen receptor diversity through the targeted activity of the RAG1/2 recombinase, but the extent to which RAG also engages cryptic genomic targets during normal lymphocyte development remains poorly defined. Here, we developed a targeted PCR-sequencing approach to detect and quantify rare RAG-mediated rearrangements in mouse thymocytes. We first examined the TCRβ locus and found that four of its twelve pseudogenes undergo detectable rearrangement in vivo, despite being considered non-functional components of the repertoire. Extending this analysis across the locus revealed 33 previously uncharacterized cryptic recombination sites involved in non-functional rearrangements with DJβ segments. These events occurred across both the Vβ region and the largely inaccessible Vβ30–Dβ1 intergenic region, with individual cryptic sites spanning a broad range of recombination frequencies. Cryptic sites were highly heterogeneous in sequence and chromatin context: neither RSS resemblance, predicted Z-DNA formation, local epigenetic features, nor chromosomal interactions reliably distinguished sites with detectable recombination from those at which recombination was not detected. We further identified additional cryptic RAG-mediated rearrangements at the Bcl11b locus, demonstrating that such events are not restricted to antigen receptor loci. Together, these findings reveal an unexpectedly broad landscape of low-frequency RAG-mediated DNA rearrangement in developing T lymphocytes and suggest that cryptic target selection cannot be explained solely by the local genetic and epigenetic features examined here.",
  "abstract_shown": true,
  "affiliations": [
    "The Pirbright Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "D. Sobral"
    },
    {
      "name": "J. Silva"
    },
    {
      "name": "D. Santos"
    },
    {
      "name": "J. Perreira Leal"
    },
    {
      "name": "J. Demengeot"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Bonnet-Di Placido"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e29syqg7vbydw.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.01.748595",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748595v1.full",
  "id": "e29syqg7vbydw",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748595v1",
  "language": null,
  "licence": "PDM-1.0",
  "licence_label": "Public domain",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/publicdomain/mark/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7208812346",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748595v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e29syqg7vbydw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "10.64898/2026.09.01.748595",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748595v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Widespread cryptic RAG-mediated recombination in developing T lymphocytes",
  "title_text": "Widespread cryptic RAG-mediated recombination in developing T lymphocytes",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:33Z",
  "url": "https://research.draconitic.com/paper/e29syqg7vbydw",
  "venue": "bioRxiv",
  "versions": []
}