Excision repair cross-complementation group 5 – General transcription factor IIH complex (ERCC5-TFIIH)

The Excision repair cross-complementation group 5 – General transcription factor IIH (ERCC5-TFIIH) complex is a multi-protein assembly essential for genomic stability and gene expression. ERCC5, also known as XPG, is a structure-specific endonuclease that performs the critical 3' incision during nucleotide excision repair (NER) to remove bulky DNA adducts, such as those caused by ultraviolet radiation or platinum-based chemotherapy (UniProt P28748). The TFIIH complex, consisting of ten subunits including the helicases XPB and XPD, acts as a central hub that unwinds DNA and recruits ERCC5 to the repair site (PubMed: 24501415). Beyond repair, this complex is indispensable for the initiation of RNA polymerase II-mediated transcription. Mutations in the components of this complex are the underlying cause of severe genetic disorders, including Xeroderma Pigmentosum (XP), Cockayne Syndrome (CS), and Trichothiodystrophy (TTD), which are characterized by extreme sun sensitivity, premature aging, and developmental delays (NIH: Gene ID 2073). In oncology, the ERCC5-TFIIH complex is a target for therapeutic sensitization; inhibiting its function can prevent cancer cells from repairing DNA damage, thereby enhancing the efficacy of DNA-targeting drugs like cisplatin (PubMed: 25512560). Current pharmacological efforts include the use of CDK7 inhibitors (e.g., Samuraciclib) and XPB inhibitors (e.g., Triptolide) to disrupt the complex's activity in malignant cells (ClinicalTrials.gov: NCT03363893).

Other names

XPG-TFIIH complexERCC5-GTF2H complexXeroderma pigmentosum group G-TFIIH complexXPG-General transcription factor IIH complex

Inhibition of nucleotide excision repair (NER) to sensitize cells to DNA-damaging agents; inhibition of RNA polymerase II-mediated transcription to induce apoptosis in cancer cells.