TFIIHc

TFIIH is a large, multi-subunit transcription factor that plays a crucial role in the initiation and promoter clearance phases of eukaryotic transcription by RNA polymerase II. It is a key component of the general transcription factor (GTF) machinery, acting at the pre-initiation complex (PIC) assembly stage. TFIIH possesses two distinct subcomplexes: a core complex and a transcription/DNA repair module. The core complex, consisting of XPB, XPD, and p44 subunits, is responsible for the ATP-dependent unwinding of the DNA double helix at the transcription start site. XPB is a DNA helicase that unwinds the DNA, while XPD is another helicase that also possesses 3'-5' exonuclease activity.

The transcription/DNA repair module, also known as the cyclin-dependent kinase (CDK)-activating kinase (CAK) module, comprises CDK7, Cyclin H, and MAT1. This module phosphorylates the C-terminal domain (CTD) of the largest subunit of RNA polymerase II, known as RPB1. This phosphorylation is essential for the transition from transcription initiation to elongation and also plays a role in recruiting other factors involved in RNA processing. Beyond transcription, TFIIH is also intimately involved in DNA repair, particularly in nucleotide excision repair (NER). The XPB and XPD helicases, in their roles within TFIIH, facilitate the unwinding of damaged DNA, allowing for the removal of damaged segments and subsequent repair. Mutations in TFIIH subunits are associated with several human diseases, including xeroderma pigmentosum and Cockayne syndrome, highlighting its critical functions in both transcription and DNA repair.