{
  "abstract": "Gene transcription by RNA Polymerase II (Pol II) is highly vulnerable to transcription-blocking DNA lesions (TBLs), which, if unresolved, induce transcription stress leading to cellular decline and aging. TBLs are removed by transcription-coupled nucleotide excision repair (TC-NER). TC-NER is initiated when Cockayne syndrome group B protein recognizes lesion-stalled Pol II and promotes TC-NER complex assembly. This complex recruits TFIIH for lesion verification, followed by incision and repair to enable transcription restart. Many TBLs stall Pol II within its active site, shielding the lesion from repair and requiring Pol II processing to expose it. However, whether this occurs through Pol II backtracking or release from the DNA, and the regulatory mechanisms involved, remain poorly defined. Here, we identified the Integrator complex as a key factor in lesion-stalled Pol II processing. Interaction proteomics revealed Integrator recruitment to late-stage TC-NER complexes. Integrator’s endonuclease core promotes efficient transcription recovery after TBL induction, without affecting lesion removal by TC-NER. Live-cell imaging and chromatin retention assays demonstrated that Integrator facilitates Pol II release from DNA following TC-NER. Collectively, these findings support a two-step mechanism for Pol II clearance during TC-NER, wherein TFIIH-mediated backtracking exposes the lesion for repair, followed by Integrator-mediated Pol II release to restore transcription.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center , 3015 GD,Rotterdam ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Cindy M A Blom"
    },
    {
      "affs": [
        0
      ],
      "name": "Emilio Gómez-Vázquez"
    },
    {
      "affs": [
        0
      ],
      "name": "Marjolein van Sluis"
    },
    {
      "affs": [
        0
      ],
      "name": "Jurgen A Marteijn",
      "orcid": "0000-0001-9321-518X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3phpr6f4fp0sx.bib",
  "cited_by": 0,
  "doi": "10.1093/nar/gkag1068",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13722877/?tool=EBI",
  "id": "3phpr6f4fp0sx",
  "issns": [
    "0305-1048",
    "1362-4962"
  ],
  "landing_url": "https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1068/9005798",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "AcademicSubjects/SCI00010"
    ],
    [
      "heading",
      "Genome Integrity, Repair and Replication"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://academic.oup.com/nar/article-pdf/54/20/gkag1068/72640301/gkag1068.pdf",
  "pmcid": "PMC13722877",
  "pmid": "42965289",
  "published": "2026-10-31",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/3phpr6f4fp0sx.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:18Z",
      "native_id": "10.1093/nar/gkag1068",
      "source": "crossref",
      "url": "https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1068/9005798"
    },
    {
      "first_seen": "2026-11-02T03:21:51Z",
      "native_id": "PMC:PMC13722877",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13722877"
    },
    {
      "first_seen": "2026-11-04T12:21:37Z",
      "native_id": "PMC13722877",
      "source": "pmc",
      "url": "https://doi.org/10.1093/nar/gkag1068"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:0305-1048",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Integrator complex removes lesion-stalled RNA polymerase II after transcription-coupled repair to facilitate transcription restart",
  "title_text": "Integrator complex removes lesion-stalled RNA polymerase II after transcription-coupled repair to facilitate transcription restart",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:37Z",
  "url": "https://research.draconitic.com/paper/3phpr6f4fp0sx",
  "venue": "Nucleic Acids Research",
  "versions": []
}