XPB

XPB is a DNA helicase encoded by the ERCC3 gene in humans. It is a core component of the transcription factor IIH (TFIIH) complex, which participates in both transcription initiation and nucleotide excision repair. XPB and XPD helicases within TFIIH provide complementary DNA unwinding activities that support promoter opening for RNA polymerase II-driven transcription and, in response to DNA damage, the incision steps of nucleotide excision repair.

In transcription, TFIIH helps unwind promoter DNA to form the open complex, allowing RNA polymerase II to begin RNA synthesis. XPB contributes ATP-dependent helicase activity that powers this opening. In nucleotide excision repair, TFIIH is recruited to sites of DNA damage and assists in verifying lesions and unwinding DNA around the lesion to permit endonucleases to remove a damaged oligonucleotide.

Mutations in ERCC3, the gene encoding XPB, cause xeroderma pigmentosum group B, usually inherited in an autosomal recessive manner. Patients show extreme sensitivity to ultraviolet light, pigmentary abnormalities, and a markedly increased risk of skin cancer; some cases display features overlapping with Cockayne syndrome due to transcription-coupled repair defects.

XPB is evolutionarily conserved and essential for viability in model systems. It is a target of chemical inhibitors such as triptolide, which block ATPase activity and transcription in research and, in some contexts, cancer therapy. Understanding XPB informs studies of transcriptional regulation, DNA repair, and nucleotide excision repair–related diseases.