TFIIH (Transcription Factor II H) is a multi-subunit protein complex that plays a dual role in cells:
- It is essential for transcription initiation by RNA polymerase II (Pol II).
- It is also critical in nucleotide excision repair (NER), a process that fixes DNA damage.
Because of this dual functionality, TFIIH is a key player in both gene expression and genome maintenance.
🔑 Definition:
TFIIH is a general transcription factor required for the initiation of transcription by RNA polymerase II and is also involved in DNA repair via nucleotide excision repair (NER). It functions as a helicase and kinase complex.
🔬 Structure:
TFIIH is composed of 10 subunits, grouped into two main functional modules:
| Module | Key Functions | Key Subunits |
|---|---|---|
| Core complex | DNA helicase activity (unwinds DNA) | XPB, XPD, p62, p52, p44, p34, p8 |
| CAK complex | Kinase activity (phosphorylates RNA Pol II) | CDK7, Cyclin H, MAT1 |
- XPB and XPD: helicase subunits (also involved in DNA repair)
- CDK7: cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of RNA polymerase II
🧬 Role in Transcription:
During transcription initiation:
- TFIIH is recruited to the pre-initiation complex (PIC) at the promoter.
- XPB unwinds DNA at the transcription start site.
- CDK7 phosphorylates the CTD of RNA polymerase II, allowing the polymerase to transition from initiation to elongation.
🧪 Role in DNA Repair (NER):
TFIIH is also involved in nucleotide excision repair, which corrects:
- UV-induced damage (e.g., thymine dimers)
- Bulky DNA adducts
In NER:
- TFIIH is recruited to the site of damage.
- XPB and XPD helicases unwind the DNA around the lesion.
- Other enzymes excise and replace the damaged DNA.
🧠 Why TFIIH Is Important:
| Function | Significance |
|---|---|
| Transcription | Initiates and regulates RNA synthesis |
| DNA repair | Maintains genome integrity by repairing damaged DNA |
| Disease relevance | Mutations in TFIIH subunits are linked to genetic disorders |
⚠️ Clinical Relevance:
| Disorder | Cause/Connection |
|---|---|
| Xeroderma pigmentosum (XP) | Mutation in XPD → defective DNA repair → UV sensitivity |
| Trichothiodystrophy (TTD) | Mutations in XPB/XPD → brittle hair, developmental issues |
| Cockayne syndrome (CS) | Involves TFIIH-related repair dysfunction |
📌 Summary:
TFIIH is a vital protein complex with two jobs: helping start transcription and helping fix DNA damage. Through its helicase and kinase activities, TFIIH ensures that cells can express genes properly and maintain DNA integrity, making it essential for normal growth, development, and protection from DNA-damaging agents.