Transcription factor II H

Transcription Factor II H (TFIIH) is a multi-subunit protein complex that plays a crucial role in eukaryotic transcription and DNA repair. It is involved in the initiation of transcription by RNA polymerase II and is also essential for nucleotide excision repair (NER), a mechanism that repairs damaged DNA.

Structure

TFIIH is composed of ten subunits, which are organized into two distinct complexes: the core complex and the cyclin-dependent kinase (CDK)-activating kinase (CAK) complex. The core complex includes subunits such as XPB, XPD, p62, p52, p44, and p34, while the CAK complex consists of CDK7, cyclin H, and MAT1. The CAK complex is involved in the regulation of the cell cycle and transcription.

Function

Transcription

In transcription, TFIIH is part of the preinitiation complex that assembles at the promoter region of genes. It is responsible for unwinding the DNA double helix, allowing RNA polymerase II to access the template strand and begin RNA synthesis. The helicase activity of the XPB and XPD subunits is critical for this process.

DNA Repair

TFIIH is also a key player in nucleotide excision repair, a pathway that removes bulky DNA lesions such as those caused by ultraviolet (UV) light. In NER, TFIIH unwinds the DNA around the lesion, allowing other repair proteins to excise the damaged strand and fill in the gap with newly synthesized DNA.

Clinical Significance

Mutations in the genes encoding TFIIH subunits can lead to several genetic disorders, including xeroderma pigmentosum (XP), trichothiodystrophy (TTD), and Cockayne syndrome (CS). These conditions are characterized by increased sensitivity to UV light and a predisposition to skin cancers, among other symptoms.

Related Pages

• RNA polymerase II
• Nucleotide excision repair
• Xeroderma pigmentosum
• Trichothiodystrophy
• Cockayne syndrome

References

• Schaeffer, L., et al. (1993). "DNA repair helicase: a component of BTF2 (TFIIH) basic transcription factor." Science, 260(5104), 58-63.
• Coin, F., et al. (2007). "Nucleotide excision repair: from E. coli to man." Biochimie, 89(6-7), 725-733.

External Links

• TFIIH in transcription and DNA repair