TFIIH

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TFIIH is a [[General transcription factor|general transcription factor]] (GTF) involved in PIC ([[Pre-Initiation Complex|Pre-Initiation Complex]]) assembly, it is added in the last stage of assembly close to the start site of transcription. The [[Helicase|helicase]] activity of TFIIH separates the template [[DNA|DNA]] strand at the start site of [[Transcription|transcription]], forming an open complex, this requires ATP hydrolysis. TFIIH has 9 subunits and main functions include:
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TFIIH is a [[General transcription factor|general transcription factor]] (GTF) involved in PIC ([[Pre-Initiation Complex|Pre-Initiation Complex]]) assembly.&nbsp; 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|PIC assembly]] as it attaches after TFIIE has attached.&nbsp;<br>
  
1. Promotor melting and clearance
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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.&nbsp;
  
2. CTD kinase activity
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As [[RNA polymerase II|RNA polymerase II]] begins transcribing, [[TFIIH|TFIIH]] is released from the complex along with [[TFIIB|TFIIB]] and [[TFIIE|TFIIE]].&nbsp;
  
3. DNA repair coupling
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== TFIIH Function ==
  
As RNA &nbsp;polymerase II begins transcribing, TFIIH is released from the complex along with TFIIB and TFIIE.&nbsp;
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The key function of TFIIH is its involvement in the assembly of the PIC.&nbsp; It is recruited to the complex once TFIIE has been recruited and binds on the +1 transcription start site.&nbsp; 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.&nbsp; The TFIIH requires the hydrolysis of ATP to provide the energy needed for it to locally melt the DNA strands.&nbsp;
  
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).&nbsp;
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TFIIH is also involved in DNA repair and CTD kinase activity.&nbsp;
  
Mutations in the TFIIH molecule can result in three distinct genetic diseases;&nbsp;
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== TFIIH Structure ==
  
1. Xeroderma pigmentosum<br>2. Trichothiodystrophy<br>3. Cockayne Syndrome<br>
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[[TFIIH|TFIIH]] has between 9 and 10 subunits which can be divided into two parts: core and [[CAK|CAK]] modules.  
  
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The core section of the GTF contains several [[DNA helicase|DNA helicases]] including [[XPD|XPD]] and [[XPB|XPB]]. XPB plays a major role in promotor melting.
  
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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.
  
<span class="Apple-style-span" style="font-size: 1px;">
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The CAK and Core modules have the ability to dissosciate away from one another and form two separate operating units.&nbsp; On its own CAK plays a key role in the regulation of the cell cycle as well as having multiple other functions.&nbsp;
</span>
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== Mutations in TFIIH &nbsp; ==
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Mutations in the TFIIH molecule can result in three distinct genetic diseases;&nbsp;
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#[[Xeroderma pigmentosum|Xeroderma pigmentosum]]
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#[[Trichothiodystrophy|Trichothiodystrophy]]
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#[[Cockayne Syndrome|Cockayne Syndrome]]<br>
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TFIIH can also bind to the acidic domains of VP16 (herpes virus) and [[P53|p53]] (involved in apoptosis).

Latest revision as of 09:29, 24 October 2018

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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