General transcription and DNA repair factor IIH helicase subunit XPD (XPD (ERCC2))

General transcription and DNA repair factor IIH helicase subunit XPD (XPD, ERCC2) is an ATP-dependent 5’-3’ DNA helicase that is a core component of the TFIIH complex, which is essential for transcription initiation and nucleotide excision repair (NER) of DNA damage. XPD unwinds DNA at the site of lesions, facilitating repair and maintaining genomic stability. It functions structurally within TFIIH, bridging the CDK-activating kinase subcomplex to core TFIIH, and its helicase activity is required for DNA repair but dispensable for transcription itself. XPD mutations cause inherited diseases such as xeroderma pigmentosum (XP-D), trichothiodystrophy (TTD), and Cockayne syndrome, characterized by cancer susceptibility, developmental defects, and photosensitivity[1][2][3][4][5][6]. XPD also interacts with several TFIIH subunits and contains a unique FeS cluster required for its helicase function. Loss-of-function or altered activity in XPD impairs DNA repair and can sensitize cells to DNA-damaging agents and chemotherapy, making it both a biomarker for treatment response and a potential therapeutic target.

Other names

ERCC2XPDCTFIIH subunit XPDBTF2 p80TFIIH 80 kDa subunitTFIIH p80MAGEM9MGC102762MGC126218MGC126219Basic transcription factor 2 80 kDa subunitCXPDDNA 5'-3' helicase XPDDNA excision repair protein ERCC-2DNA repair protein complementing XP-D cellsTFIIH basal transcription factor complex 80 kDa subunitXeroderma pigmentosum group D-complementing proteinexcision repair cross-complementing rodent repair deficiency, complementation group 2 proteinTFIIH basal transcription factor complex helicase XPB subunitCOFS2TTDTTD1

Potential drug mechanism: inhibition of helicase activity (theoretical, not clinically established) Drugs modifying DNA repair sensitivity: platinum-based agents (e.g., cisplatin) where ERCC2 loss-of-function increases sensitivity[1][2]