{
  "id": 6780558,
  "title": "Helicase-deficient TFIIH causes severe disease features via persistent DNA excision without damage removal",
  "url": "https://urgent.news/2026/09/11/helicase-deficient-tfiih-causes-severe-disease-features-via",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-11T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.05.749590v1?rss=1"
  },
  "original_language": "en",
  "account": "Nucleotide excision repair (NER) is a process that removes helix-distorting DNA lesions, involving the TFIIH complex composed of ten subunits. XPB and XPD translocase/helicase activities within TFIIH unwind DNA to enable damage verification and endonucleolytic DNA incisions. While most XPD mutations result in xeroderma pigmentosum, specific helicase-deficient mutations lead to severe Cockayne syndrome (CS) features, such as progressive neurodegeneration, with unclear underlying causes. This study demonstrates that loss of XPD helicase activity traps TFIIH in a repetitive repair cycle, where DNA is incised at the wrong position, resulting in repeated DNA excision and resynthesis without removal of the lesion. Using C. elegans as a model organism, the research reveals that this futile DNA excision cycle induces severe neuronal dysfunction in vivo, which depends on transcription-coupled NER activity. Importantly, this detrimental effect can be mitigated by preventing the recruitment of helicase-deficient TFIIH. The findings suggest that NER incisions can occur without XPD-mediated damage verification, and persistent futile DNA excision cycles can cause severe disease features, implying that persistent NER intermediates are more pathogenic than unrepaired DNA lesions.",
  "summary": "Nucleotide excision repair (NER) removes helix-distorting DNA lesions through the ten subunit TFIIH complex, whose XPB and XPD translocase/helicase activities unwind DNA to enable damage verification and subsequent endonucleolytic DNA incisions. While most XPD mutations cause xeroderma pigmentosum, specific helicase-deficient mutations cause severe Cockayne syndrome (CS) features, including…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}