TFIIH - a Pivotal Regulatory Protein Complex

TFIIH is a multi-protein complex consisting of at least eight different subimits (review Drapkin and Reinberg, 1994 Svjestrup et al, 1996). 

A more in-depth characterization of the subimits brought surprising results. Some of the polypeptides of TFIIH could be identified as proteins shown in other experiments to participate in repair of DNA damage, as well as in the regulation of the cell cycle (CDK7/Cyclin H, see above). TFIIH itself, or other individual components of TFIIH, thus participate in the following fundamental processes in the cell  

The picture of the structure and function of TFIIH is a varied and complex one. The mechanistic details are long not imderstood. 

TFIIH is required for critical, early steps of transcription, including the transition from initiation to elongation. In addition to its function in phosphorylating the CTD, TFIIH opens the DNA template by its ATP-dependent helicase activities located on the XPB and XPD proteins. Electron microscope studies have revealed a ring-like structure of TFIIH, with a hole whose size is able to accommodate a double-stranded DNA (Chang and Kornberg, 2000). 

TFIIH also partidpates in another important cellular function, namely nucleotide excision repair of damaged DNA. This function accounts for the observation that transcription and the removal of bulky base adducts by nucleotide excision repair (NER) are coupled. An increased repair of DNA damage by NER is observed while a gene is being transcribed. During transcription-coupled repair, TFIIH assembles with other repair proteins into a large repair complex, allowing for the removal of DNA adducts. 

The presence of the protein kinase CDK7 and of Cyclin H in the kinase subcomplex indicates a link between transcription and cell cycle regulation. CDK7 is identical to cyclin-activating kinase, CAR (see Sectionl3.2.1), which regulates cell cycle transitions. 

TFIIH itself, or other individual components of TFIIH, thus participate in the following fundamental processes in the cell  

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