{
  "abstract": "DNA double-strand break repair often involves end resection, yet how resected ends are directed toward distinct repair pathways remains poorly understood. Here, we identify replication protein A (RPA) as an unexpected essential factor for cellular polymerase theta-mediated end joining (TMEJ). Using MUSIC-MAP, a newly developed platform linking endogenous sequence variants to DNA repair outcomes, we map a discrete functional interface between RPA2 and polymerase theta (Pol{theta}). Disrupting this interface in RPA2 abolishes TMEJ without impairing cell viability or homologous recombination. Mutations in the complementary Pol{theta} surface likewise impair TMEJ, whereas reciprocal charge-reversal mutations in RPA2 and Pol{theta} restore TMEJ, providing genetic evidence for a direct physical interaction. Structural modeling suggests that the Pol{theta}-binding surface becomes accessible at RPA-coated ssDNA termini, positioning RPA as a docking platform for Pol{theta} engagement. These findings reveal how RPA, previously considered a barrier to TMEJ, instead functions as a molecular platform that translates the organization of ssDNA into selective enzyme engagement, enabling mutagenic repair without compromising homologous recombination.",
  "abstract_shown": true,
  "affiliations": [
    "Leiden University Medical Center"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "M. Barazas"
    },
    {
      "name": "C. I. Bos"
    },
    {
      "name": "H. Kool"
    },
    {
      "name": "J. Schimmel"
    },
    {
      "name": "R. van Schendel"
    },
    {
      "name": "M. S. Luijsterburg"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Tijsterman"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c3c82jjfba343.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.25.761560",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.25.761560v1.full",
  "id": "c3c82jjfba343",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.25.761560v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "molecular biology"
    ],
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7223918144",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.25.761560v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c3c82jjfba343.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:51Z",
      "native_id": "10.64898/2026.10.25.761560",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.25.761560v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A direct RPA-Polθ interaction licenses theta-mediated end joining",
  "title_text": "A direct RPA-Polθ interaction licenses theta-mediated end joining",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:51Z",
  "url": "https://research.draconitic.com/paper/c3c82jjfba343",
  "venue": "bioRxiv",
  "versions": []
}