TFIIH

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TFIIH is a general transcription factor (GTF) involved in PIC (Pre-Initiation Complex) assembly, it is added in the last stage of assembly close to the start site of transcription. The helicase activity of TFIIH separates the template DNA strand at the start site of transcription, forming an open complex, this requires ATP hydrolysis. TFIIH has 9 subunits and main functions include:

  1. Promotor melting and clearance
  2. CTD kinase activity
  3. DNA repair coupling

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

TFIIH can be divided into two parts: core and CAK. 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 can dissociated away from the TFIIH molecule where it has other functions in the cell cycle (cdk activating kinases). The CAK module also contains one of the kinases that is involved in hosphorylation of the CTD (C-terminal domain) of RNA polymerase II. This phosphorylation is needed for promotor clearance. 

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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