{
  "abstract": "DNA lesions can stall replication, generating ssDNA gaps that require filling to maintain genome stability. The E3 ubiquitin ligase RFWD3/FANCW targets RPA and PCNA to regulate replication dynamics and damage tolerance, but its roles in these processes and influence on cell mutability remain incompletely understood. Here, we show that RFWD3 prevents the accumulation of ssDNA gaps in UV-irradiated cells through its E3 ligase activity and interaction with RPA. Mutational signature analysis implicates RFWD3 in the spontaneous mutability of human cells and reveals its involvement in 6-4 photoproducts tolerance. Accordingly, photorepair of 6-4 photoproducts, but not of cyclobutane pyrimidine dimers, alleviates gap accumulation in RFWD3-depleted cells. RFWD3 KO has limited impact on PCNA ubiquitylation, but its depletion sharply decreases UV-induced RPA ubiquitylation. Moreover, cells expressing an RPA mutant that cannot be ubiquitylated accumulate ssDNA gaps epistatically with RFWD3 loss. We propose that RFWD3-dependent RPA ubiquitylation regulates post-replicative ssDNA gaps to promote helix-distorting lesion tolerance.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 28,
  "authors": [
    {
      "name": "Lisa Casimir",
      "orcid": "0000-0001-9526-9712"
    },
    {
      "name": "Isabelle Marois"
    },
    {
      "name": "Félix Racine-Brassard",
      "orcid": "0000-0002-5202-7550"
    },
    {
      "name": "Jean-Christophe Dubois"
    },
    {
      "name": "Félix Goudreau"
    },
    {
      "name": "Maïlyn Yates",
      "orcid": "0000-0002-5110-4622"
    },
    {
      "name": "Rima Kochman"
    },
    {
      "name": "Billel Djerir"
    },
    {
      "name": "Samuel Zimmer"
    },
    {
      "name": "Yosra Mehrjoo",
      "orcid": "0009-0007-0807-7378"
    },
    {
      "name": "Alexandra Octaviana Szenti"
    },
    {
      "name": "Vincent Mimee"
    },
    {
      "name": "François Bélanger"
    },
    {
      "name": "Andréanne Blondeau"
    },
    {
      "name": "Gaëlle Lescalet"
    },
    {
      "name": "Edlie St-Hilaire"
    },
    {
      "name": "Wendy Leung"
    },
    {
      "name": "Ryan M. Baxley",
      "orcid": "0000-0002-3286-7990"
    },
    {
      "name": "Nadia Côté"
    },
    {
      "name": "Luc Gaudreau"
    },
    {
      "name": "Anja Katrin Bielinsky",
      "orcid": "0000-0003-1783-619X"
    },
    {
      "name": "Laurent Cappadocia",
      "orcid": "0000-0001-7348-1982"
    },
    {
      "name": "Elliot Drobetsky",
      "orcid": "0000-0002-0991-4314"
    },
    {
      "name": "Amélie Fradet-Turcotte",
      "orcid": "0000-0002-5431-8650"
    },
    {
      "name": "Stéphane Coulon",
      "orcid": "0000-0001-8090-914X"
    },
    {
      "name": "Hugo Wurtele",
      "orcid": "0000-0002-5733-1711"
    },
    {
      "name": "Pierre-Étienne Jacques",
      "orcid": "0000-0002-3961-294X"
    },
    {
      "name": "Alexandre Maréchal",
      "orcid": "0000-0003-3216-6542"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dzrjvwwfnfqff.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78252-y",
  "fulltext_url": "https://europepmc.org/articles/PMC13728104",
  "id": "dzrjvwwfnfqff",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-78252-y",
  "language": "eng",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7220436374",
  "pdf_url": "https://www.nature.com/articles/s41467-026-78252-y_reference.pdf",
  "pmcid": "PMC13728104",
  "pmid": "42971966",
  "published": "2026-10-05",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/dzrjvwwfnfqff.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:38Z",
      "native_id": "10.1038/s41467-026-78252-y",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41467-026-78252-y"
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      "first_seen": "2026-11-06T12:23:51Z",
      "native_id": "PMC13728104",
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|DNA Repair Mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "RFWD3/FANCW orchestrates post-replicative filling of ssDNA gaps to promote UV tolerance",
  "title_text": "RFWD3/FANCW orchestrates post-replicative filling of ssDNA gaps to promote UV tolerance",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:09Z",
  "url": "https://research.draconitic.com/paper/dzrjvwwfnfqff",
  "venue": "Nature Communications",
  "versions": []
}