{
  "abstract": "Cohesin is a conserved multiprotein complex (SMC1, SMC3, RAD21, and either STAG1 or STAG2) that organizes three-dimensional genome architecture and regulates chromosome segregation, gene expression, and DNA damage repair (1-4). Following double-strand breaks (DSBs), cohesin is recruited to sites of DNA damage - a process considered essential for efficient homologous recombination (5-15). Yet how DSB signaling elicits cohesin recruitment and subsequent cohesion establishment remains poorly understood. Here we show that telomere replication stress activates de novo STAG2-cohesin loading, thereby promoting break-induced telomeric DNA repair. We demonstrate that this DNA break-elicited cohesin recruitment is strictly controlled by the BRCT domain-containing DNA damage recognition factor PAXIP1 and its functional partner PAGR1. Cryo-electron microscopy structure reveals that PAGR1, together with PAXIP1, physically binds to a composite interface formed by the STAG2-RAD21 cohesin subcomplex. Complementary mutational and biochemical analyses define the molecular basis of this interaction and establish its essential role in break-induced cohesion establishment. Furthermore, we show that PAXIP1-PAGR1-enacted STAG2-cohesin recruitment complements with the PML body-associated pathway in orchestrating break-induced alternative lengthening of telomeres (ALT). Concurrent depletion of PML together with PAXIP1, PAGR1 or STAG2 disrupts ALT-mediated telomere maintenance, leading to end-to-end chromosomal fusion and mitotic cell death. Collectively, these findings uncover a distinctive molecular mechanism through which DSB signaling directs de novo cohesion establishment, and highlight its critical importance in break-induced telomere repair.",
  "abstract_shown": true,
  "affiliations": [
    "Weill Cornell Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "name": "S. Y. Hwang"
    },
    {
      "name": "X. Wu"
    },
    {
      "name": "X. Huang"
    },
    {
      "name": "F. LI"
    },
    {
      "name": "Z. Wang"
    },
    {
      "name": "E. Y. Yu"
    },
    {
      "name": "Y. Xu"
    },
    {
      "name": "Z. Zhang"
    },
    {
      "name": "I. Moon"
    },
    {
      "name": "S.-A. Kim"
    },
    {
      "name": "B. Yamrom"
    },
    {
      "name": "S. Yang"
    },
    {
      "name": "Y. Wang"
    },
    {
      "name": "Y. Kwon"
    },
    {
      "name": "N. Lue"
    },
    {
      "name": "J. Paik"
    },
    {
      "name": "C. Dong"
    },
    {
      "affs": [
        0
      ],
      "name": "H. Zheng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eg66zn2sxzgam.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.14.751543",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751543v1.full",
  "id": "eg66zn2sxzgam",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751543v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "molecular biology"
    ],
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7213457356",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751543v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/eg66zn2sxzgam.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:49Z",
      "native_id": "10.64898/2026.09.14.751543",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.14.751543v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "PAXIP1-PAGR1 directs cohesin recruitment during break-induced telomere repair",
  "title_text": "PAXIP1-PAGR1 directs cohesin recruitment during break-induced telomere repair",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:49Z",
  "url": "https://research.draconitic.com/paper/eg66zn2sxzgam",
  "venue": "bioRxiv",
  "versions": []
}