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General transcription and DNA repair factor IIH helicase subunit XPB (XPB/ERCC3) is an ATP-dependent DNA helicase that is a critical part of the TFIIH complex, which has dual roles in the initiation of RNA polymerase II-dependent gene transcription and in nucleotide excision DNA repair. XPB unwinds DNA with 3'-5' polarity to facilitate repair and transcription, acting as a wedge to open DNA strands at sites of damage and at promoters for gene activation[1][2][3][4]. Mutations in XPB/ERCC3 are associated with several genetic syndromes characterized by photosensitivity, abnormal development, and markedly increased cancer risk, reflecting its essential function in genome maintenance; small molecules such as triptolide may selectively inhibit XPB for potential cancer therapy, but this raises substantial safety and selectivity concerns because of XPB’s central role in cellular homeostasis[1][2][3].
Inhibition of TFIIH complex activity, preventing promoter opening and transcription initiation (triptolide); Blocking DNA unwinding and hence hindering DNA repair and gene transcription
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