TFIIH formation

The binding of TFIIH completes the formation of the pre-initiation complex. TFIIH is a multi-protein complex with a variable composition (see 1.4.2.5) and which possesses protein kinase, ATPase and heUcase activities. The heUcase activity of TFIIH is required for the melting of the promoter. 

Diverse Functions of TFIIH In eukaryotes, the repair of damaged DNA (see Table 25-5) is more efficient within genes that are actively being transcribed than for other damaged DNA, and the template strand is repaired somewhat more efficiently than the nontemplate strand. These remarkable observations are explained by the alternative roles of the TFIIH subunits. Not only does TFIIH participate in the formation of the closed complex during assembly of a transcription complex (as described above), but some of its subunits are also essential components of the separate nucleotide-excision repair complex (see Fig. 25-24). 

The increase in nuclear cyclin B/CDKl activity promotes phosphorylation of nuclear substrates that are necessary for mitosis, such as nuclear envelope breakdown, spindle formation, chromatin condensation, and restmcturing of the Golgi and endoplasmic reticulum (85, 86). Numerous cyclin B/CDKl substrates have been dehned, which include nuclear lamins, nucleolar proteins, centrosomal proteins, components of the nuclear pore complex, and microtubule-associated proteins (87-89). Cyclin B/CDKl complexes also phosphorylate MCM4 to block replication of DNA, the TFIIH subunit of RNA polymerase II to inhibit transcription, and the ribosomal S6 protein kinase to prevent translation during mitosis (90-92). 

Transcription initiation begins by the formation of a preinitiation complex, and most of the control of transcription occurs at this step. This complex normally contains RNA polymerase II and six general transcription factors (GTFs)—TTHA, TFIIB, TTIID, TFIIE, TFIIF, and TFIIH. 

Its primary function is as a general transcription factor involved in the formation of the open complex for transcription initiation. It binds to the basal unit and is involved in DNA melting through a helicase activity as well as promoter clearance via phosphorylation of the CTD of RNA polymerase. In addition, it also has a cyclin-dependent kinase activity. Thus, TFIIH is involved in tying transcription and cell division together. It is also involved in DNA repair mechanisms. 

Egly,J.-M. (2001). TFIIH From transcription to clinic. FEES Lett. 24884, 124-128. Evans, E., Moggs,J. G., Hwang, J. R., Egly,J.-M., and Wood, R. D. (1997). Mechanism of open complex and dual incision formation by human nucleotide excision repair factors. EMBOJ. 16, 6559-6573. 

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