{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:33:52Z","timestamp":1787027632011,"version":"build-2736575974"},"reference-count":123,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Xeroderma pigmentosum group B (XPB\/ERCC3) and group D (XPD\/ERCC2) helicases are integral components of the transcription factor IIH (TFIIH) complex, coordinating DNA unwinding during transcription initiation and nucleotide excision repair (NER). XPB functions as an ATP-driven translocase that generates torsional strain to promote promoter melting and DNA opening at lesion sites, whereas XPD acts as a 5\u2032 to 3\u2032 helicase responsible for lesion verification and extension of the repair bubble. Structural and biochemical studies have clarified how TFIIH subunits regulate these helicases\u2014p52 and p8 modulate XPB\u2019s translocation activity, while p44, p62, and MAT1 control XPD\u2019s helicase function through conformational and compositional transitions within the complex. Beyond their canonical roles, XPB and XPD participate in diverse cellular pathways, including cell-cycle regulation and oxidative stress response, highlighting their involvement in maintaining genome integrity beyond repair and transcription. Mutations in either helicase lead to xeroderma pigmentosum (XP), trichothiodystrophy (TTD), or combined XP\/Cockayne syndrome (XP\/CS) phenotypes, emphasizing the essential role of TFIIH integrity for human health. Recent biochemical and pharmacological advances have further revealed the therapeutic relevance of these helicases\u2014XPB as a target of small-molecule inhibitors such as triptolide, Minnelide, and spironolactone, and XPD as a potential modulator of cancer sensitivity to DNA-damaging treatments. Collectively, XPB and XPD exemplify the structural and functional versatility of TFIIH helicases across repair, transcription, and genome maintenance.<\/jats:p>","DOI":"10.3390\/biom16030435","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T11:12:25Z","timestamp":1773400345000},"page":"435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrating Structural, Biochemical, and Cellular Perspectives on the TFIIH Helicases XPB and XPD"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6659-5868","authenticated-orcid":false,"given":"Marco","family":"Bravo","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of California, 900 University Ave, Riverside, CA 92521, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6763-0467","authenticated-orcid":false,"given":"Li","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of California, 900 University Ave, Riverside, CA 92521, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a012609","DOI":"10.1101\/cshperspect.a012609","article-title":"Nucleotide Excision Repair in Eukaryotes","volume":"5","author":"Scharer","year":"2013","journal-title":"Cold Spring Harb. 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