TFIIH is a multi-subunit protein complex that plays a critical role in the process of transcription in eukaryotic cells. It is essential for the unwinding of DNA at the transcription start site and has functions in nucleotide excision repair, linking these two vital cellular processes. The complex is composed of both ATP-dependent helicase activity, which helps in separating the DNA strands, and kinase activity, which phosphorylates the C-terminal domain of RNA polymerase II, crucial for the transition from transcription initiation to elongation.
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TFIIH consists of ten subunits and has both helicase and kinase activities, making it essential for unwinding DNA and phosphorylating RNA polymerase II.
The helicase activity of TFIIH is particularly important as it allows the DNA strands to separate at the promoter region, enabling transcription to begin.
TFIIH also plays a significant role in nucleotide excision repair, recognizing and repairing bulky DNA lesions such as those caused by UV radiation.
The phosphorylation of the C-terminal domain of RNA polymerase II by TFIIH is crucial for transitioning from transcription initiation to elongation.
Mutations in TFIIH or its subunits can lead to severe consequences, including disorders like Xeroderma Pigmentosum, which involves increased sensitivity to UV light due to defective DNA repair.
Review Questions
How does TFIIH facilitate the transition from transcription initiation to elongation?
TFIIH facilitates the transition from transcription initiation to elongation primarily through its kinase activity. After the formation of the pre-initiation complex and the unwinding of DNA, TFIIH phosphorylates the C-terminal domain of RNA polymerase II. This phosphorylation event triggers a series of conformational changes that allow RNA polymerase II to move past the promoter region and enter the elongation phase of transcription.
Discuss the dual roles of TFIIH in transcription and DNA repair, and why this is important for cellular function.
TFIIH plays a dual role in both transcription and nucleotide excision repair, making it vital for cellular health. In transcription, it helps initiate the process by unwinding DNA and modifying RNA polymerase II. In DNA repair, it recognizes and fixes damaged DNA, preventing mutations. This multifaceted functionality ensures that cells can accurately express genes while also maintaining genomic integrity, reducing the risk of diseases such as cancer.
Evaluate the impact of TFIIH mutations on human health and their connection to genetic disorders.
Mutations in TFIIH can have profound impacts on human health, leading to genetic disorders such as Xeroderma Pigmentosum (XP). XP results from defective nucleotide excision repair due to faulty TFIIH function, causing individuals to be highly sensitive to UV light and have an increased risk of skin cancers. This illustrates how essential TFIIH is not only in transcription but also in protecting genomic stability, showing that defects in this complex can lead to significant health issues.
Related terms
RNA Polymerase II: An enzyme responsible for synthesizing messenger RNA (mRNA) from a DNA template during the transcription process.
Transcription Factors: Proteins that bind to specific DNA sequences to regulate gene expression by promoting or inhibiting the recruitment of RNA polymerase.
Nucleotide Excision Repair: A DNA repair mechanism that removes and replaces damaged sections of DNA, which can be linked to the activities of TFIIH.