{
  "abstract": "The cohesin ring complex organizes and mediates functional activity of the genome through chromatin loop extrusion1,2. Cohesin comprises a core SMC1-SMC3-RAD21 ring associated with multiple regulatory proteins, including SA1 and SA2 paralogs that bind mutually-exclusively to a RAD21 site3,4. Functional studies of cohesin complexes in vivo often employ inactivation of particular components2,3. However, inactivation of SA1 or SA2 in mice is limited by mouse embryonic lethality5-7 and, for dual SA1/2-inactivation by cycling cell lethality8-10. For these reasons, it remains unknown whether the requirement for SA1/2 in loop extrusion in vitro11,12 applies in vivo1,2, and whether these factors have overlapping or distinct functions in regulating this process3. Here, we employ G0/G1-arrested v-Abl pro-B lines, which are viable in the absence of cohesin-complex factors13,14, to dissect SA1 and SA2 functions in V(D)J recombination, a strictly G0/G1-specific process that harnesses loop extrusion to effect distinct Igh and Ig{kappa} locus recombination mechanisms15,16. Robust long-range Igh or Ig{kappa} V(D)J recombination continued unabated in the absence of SA1 or SA2. However, inactivation of both abrogated most positioned chromatin loops genome-wide and also abolished long-range Igh V(D)J recombination with a phenotype similar to RAD21 (cohesin) inactivation13. Yet, robust Ig{kappa} V(D)J recombination continued upon dual SA1/2-inactivation, which along with Hi-C findings, demonstrates ongoing loop-extrusion in the absence of SA1/2. Correspondingly, replacement of weak Igh V(D)J recombination signal sequences (RSSs) that target V(D)J recombination activity, with strong Ig{kappa} counterparts15 restored long-range Igh V(D)J recombination in SA1/2 inactivated cells. We conclude that SA1/2 together maintain loop extrusion impediments and genome-wide architecture in G0/G1-arrested cells; and, in their absence, loop extrusion proceeds unimpeded. Remarkably, strong RSSs allow Ig{kappa} to function normally in the absence of internal positioned loop structure across the 3.1-mega-base Ig{kappa} locus. We discuss implications of our findings for long-range gene regulation in G0/G1-arrested cells more broadly.",
  "abstract_shown": true,
  "affiliations": [
    "Boston Children's Hospital Harvard Medical School"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "Z. Yang"
    },
    {
      "name": "Y. Fu"
    },
    {
      "name": "M. Mikhova"
    },
    {
      "name": "D. Chen"
    },
    {
      "name": "C. Hebert"
    },
    {
      "name": "A. Y. Ye"
    },
    {
      "name": "X. Lin"
    },
    {
      "name": "T. Williams"
    },
    {
      "name": "H. Hu"
    },
    {
      "name": "Z. Ba"
    },
    {
      "name": "J. Dekker"
    },
    {
      "affs": [
        0
      ],
      "name": "F. W. Alt"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/84x9fmsczn8vy.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.10.757971",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.757971v1.full",
  "id": "84x9fmsczn8vy",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.757971v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7221445290",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.757971v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/84x9fmsczn8vy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:11Z",
      "native_id": "10.64898/2026.10.10.757971",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.10.757971v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Robust V(D)J Recombination in the Absence of SA1/2-mediated Chromatin Loops",
  "title_text": "Robust V(D)J Recombination in the Absence of SA1/2-mediated Chromatin Loops",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:11Z",
  "url": "https://research.draconitic.com/paper/84x9fmsczn8vy",
  "venue": "bioRxiv",
  "versions": []
}