The role of Transcription Factor IIH complex in nucleotide excision repair

DNA damage occurs throughout life from a variety of sources, and it is imperative to repair damage in a timely manner to maintain genome stability. Thus, DNA repair mechanisms are a fundamental part of life. Nucleotide excision repair (NER) plays an important role in the removal of bulky DNA adducts, such as cyclobutane pyrimidine dimers from ultraviolet light or DNA crosslinking damage from platinum-based chemotherapeutics, such as cisplatin. A main component for the NER pathway is transcription factor IIH (TFIIH), a multifunctional, 10-subunit protein complex with crucial roles in both transcription and NER. In transcription, TFIIH is a component of the pre-initiation complex and is important for promoter opening and the phosphorylation of RNA Polymerase II (RNA Pol II). During repair, TFIIH is important for DNA unwinding, recruitment of downstream repair factors, and verification of the bulky lesion. Several different disease states can arise from mutations within subunits of the TFIIH complex. Most strikingly are xeroderma pigmentosum (XP), XP combined with Cockayne syndrome (CS), and trichothiodystrophy (TTD). Here, we summarize the recruitment and functions of TFIIH in the two NER subpathways, global genomic (GG-NER) and transcription-coupled NER (TC-NER). We will also discuss how TFIIH's roles in the two subpathways lead to different genetic disorders.

Automated summary

DNA damage is a common occurrence throughout life and repairing it promptly is essential for maintaining genome stability. The nucleotide excision repair (NER) mechanism, specifically transcription factor IIH (TFIIH) plays a crucial role in removing bulky DNA adducts and ensuring DNA unwinding, repair factor recruitment, and lesion verification. Mutations in TFIIH subunits can lead to various genetic disorders, including xeroderma pigmentosum (XP), XP combined with Cockayne syndrome (CS), and trichothiodystrophy (TTD). This article provides an overview of TFIIH and its roles in the two NER subpathways, global genomic (GG-NER) and transcription-coupled NER (TC-NER), and discusses how dysfunctions in these pathways contribute to genetic disorders.