TFIIH

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TFIIH is a general transcription factor (GTF) involved in PIC (Pre-Initiation Complex) assembly.  It is believed to be one of the key GTFs involed in PIC assembly because it separates the DNA strands allowing initiation of transcription to commence. It is the last TFII to be recruited in the PIC assembly as it attaches after TFIIE has attached. 

The name TFIIH can be broken down: TF indicates the protein is a transcription factor (in this case we also know it to be a General Transcription Factor), II shows the protein is specific to RNA Polymerase II (like I would indicate a transcription factor which was specifica to RNA polymerase I transcription initiation) and the H identifies the unique protein which is this transcription factor within this group. 

As RNA polymerase II begins transcribing, TFIIH is released from the complex along with TFIIB and TFIIE

TFIIH Function

The key function of TFIIH is its involvement in the assembly of the PIC.  It is recruited to the complex once TFIIE has been recruited and binds on the +1 transcription start site.  It plays a key role in allowing transcription initiation to occur because it uses XPB (a helicase domain of the protein) to melt the DNA locally thus allowing the RNA polymerase II to read the ssDNA as a template to begin its transcription process.  The TFIIH requires the hydrolysis of ATP to provide the energy needed for it to locally melt the DNA strands. 

TFIIH is also involved in DNA repair and CTD kinase activity. 

TFIIH Structure

TFIIH has between 9 and 10 subunits which can be divided into two parts: core and CAK modules.

The core section of the GTF contains several DNA helicases including XPD and XPB. XPB plays a major role in promotor melting.

The CAK module contains one of the kinases involved in the phosphorylation of the CTD (C-terminal domain) of RNA polymerase II which is key to allowing the RNA polymerase II to move from transcription initiation to elongation, after promoter clearance has occurred.

The CAK and Core modules have the ability to dissosciate away from one another and form two separate operating units.  On its own CAK plays a key role in the regulation of the cell cycle as well as having multiple other functions. 

Mutations in TFIIH  

Mutations in the TFIIH molecule can result in three distinct genetic diseases; 

  1. Xeroderma pigmentosum
  2. Trichothiodystrophy
  3. Cockayne Syndrome

TFIIH can also bind to the acidic domains of VP16 (herpes virus) and p53 (involved in apoptosis).

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