Transcription Factor H

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Transcription Factor H (TFIIH) is part of the eukaryotic Pre Initiation Complex which helps to position eukaryoticRNA polymerase 2 correctly at the promoter of a gene.

TFIIH is composed of 9 - 10 subunits and can be divided into 2 parts, the Core and the Cak. Located in the Core is XPB and XPD helicase subunits with are orthologs of yeast Ss12 and Rad3 [1], XPB promotes DNA unwinding which is need for the RNA to successfully transcribe the DNA to mRNA. This step is energy dependent so requires hydrolysation of ATP[2]  The Cak region has kinases which phosphorylates a serine in the fifth position of the cysteine rich domain of RNA polymerase 2, this step is essential as it causes a conformational change to tighten its interaction with the DNA and leave some of the transcription factors behind[3]. Cak can also dissociate away from TFIIH as it has other roles in cell cycle regulation.

Some diseases associated with TFIIH mutations include:

  • Xeroderma Pigmentosum (UV sensitivity)
  • Trichothiodystrophy
  • Cockayne Syndrome

References

  1. Goel Shivani, Krishnamurthy Shankarling, Hampsey Michael (2011) The mechanism of start site selection by RNA polymerase II: interplay between TFIIB and the Ssl2/XPB helicase subunit of TFIIH; J Biol Chem; [Epub ahead of print]
  2. Alberts et al. (2008) Molecular biology of the cell, 5th edition,pages;341 . garland science,madison avenue,new york.
  3. Alberts et al. (2008) Molecular biology of the cell, 5th edition,pages;341, 342 . garland science,madison avenue,new york.