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	~~'''~~Transcription Factor II H''' ('''TFIIH''') is a multifunctional protein complex essential in several critical cellular processes, including [[transcription]], [[nucleotide excision repair]] (NER), and cell cycle regulation. It plays a pivotal role in the transcription of [[gene\|genes]] by [[RNA polymerase II]], a process fundamental for the synthesis of messenger RNA (mRNA) in eukaryotic cells. Additionally, TFIIH is involved in DNA repair mechanisms, specifically in the repair of DNA damage caused by ultraviolet (UV) radiation.		== Transcription Factor II H ==

	~~==Composition and Structure==~~		'''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]].
	~~TFIIH consists of ten subunits, divided into two sub-complexes: the~~ ''~~Core~~'' ~~complex and the~~ ''~~CAK~~'' ~~(CDK~~-~~activating kinase)~~ complex~~. The Core complex includes subunits such as XPB~~ and ~~XPD, which are~~ [[~~helicase~~]]~~s responsible for unwinding DNA, and p62, p52, p44, p34, and TTDA~~. ~~The CAK complex, which~~ is involved in ~~cell cycle control, includes CDK7, cyclin H,~~ and ~~MAT1. The intricate structure of TFIIH allows it to engage in various interactions necessary~~ for ~~its diverse functions~~.

	==~~Function in Transcription~~==		== Structure ==
	During transcription initiation, TFIIH is recruited to the [[promoter]] region of a gene as part of the pre-initiation complex (PIC). The helicase activity of TFIIH unwinds the DNA, allowing RNA polymerase II to access the template strand. Furthermore, the kinase activity of the CAK complex phosphorylates the C-terminal domain (CTD) of RNA polymerase II, a modification crucial for the transition from transcription initiation to elongation.

	~~==Role in DNA Repair==~~		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.
	TFIIH~~'s involvement in nucleotide excision repair~~ (~~NER~~) ~~highlights its critical role in maintaining genomic integrity~~. ~~In NER~~, ~~TFIIH unwinds the DNA around a lesion~~, ~~such as a thymine dimer caused by UV light~~, ~~enabling~~ the ~~excision~~ of ~~the damaged strand~~ and ~~subsequent repair~~. ~~Mutations~~ in ~~TFIIH subunits, particularly in XPB and XPD, are linked to rare genetic disorders like [[Xeroderma Pigmentosum]]~~ and ~~[[Cockayne Syndrome]], which are characterized by sensitivity to UV light and increased risk of skin cancer~~.

	==~~Cell Cycle Regulation~~==		== Function ==
	The CAK complex of TFIIH also influences the cell cycle by phosphorylating several key proteins, including CDKs (cyclin-dependent kinases), which are vital for cell cycle progression. This regulatory function underscores the importance of TFIIH beyond transcription and DNA repair, highlighting its role in cell proliferation and growth.

	==~~Clinical Significance~~==		=== Transcription ===
	Given its essential functions, TFIIH is a target of interest in the study of cancer and other diseases where transcription, DNA repair, and cell cycle regulation are disrupted. Understanding the mechanisms of TFIIH action and its interactions with other cellular components may lead to novel therapeutic strategies for treating such conditions.

	==~~Research~~ and ~~Future Directions~~==		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.
	~~Ongoing research aims~~ to ~~elucidate the detailed mechanisms~~ by ~~which TFIIH functions in its various roles~~ and to ~~understand how mutations in~~ TFIIH ~~components contribute~~ to ~~disease~~. ~~Advances in structural biology techniques~~, ~~such as cryo~~-~~electron microscopy~~, ~~have provided insights into the architecture of~~ TFIIH and ~~its interactions within the cell, offering potential avenues for drug development.~~
			=== 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 ==

			* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1234567/ TFIIH in transcription and DNA repair]

	[[Category:Transcription factors]]		[[Category:Transcription factors]]
	[[Category:DNA repair]]		[[Category:DNA repair]]
	~~[[Category:Cell cycle]]~~

	~~{{Molecular-cell-biology-stub}}~~
	~~{{Medicine-stub}}~~

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'''Transcription Factor II H''' ('''TFIIH''') is a multifunctional protein complex essential in several critical cellular processes, including [[transcription]], [[nucleotide excision repair]] (NER), and cell cycle regulation. It plays a pivotal role in the transcription of [[gene|genes]] by [[RNA polymerase II]], a process fundamental for the synthesis of messenger RNA (mRNA) in eukaryotic cells. Additionally, TFIIH is involved in DNA repair mechanisms, specifically in the repair of DNA damage caused by ultraviolet (UV) radiation.

==Composition and Structure==
TFIIH consists of ten subunits, divided into two sub-complexes: the ''Core'' complex and the ''CAK'' (CDK-activating kinase) complex. The Core complex includes subunits such as XPB and XPD, which are [[helicase]]s responsible for unwinding DNA, and p62, p52, p44, p34, and TTDA. The CAK complex, which is involved in cell cycle control, includes CDK7, cyclin H, and MAT1. The intricate structure of TFIIH allows it to engage in various interactions necessary for its diverse functions.

==Function in Transcription==
During transcription initiation, TFIIH is recruited to the [[promoter]] region of a gene as part of the pre-initiation complex (PIC). The helicase activity of TFIIH unwinds the DNA, allowing RNA polymerase II to access the template strand. Furthermore, the kinase activity of the CAK complex phosphorylates the C-terminal domain (CTD) of RNA polymerase II, a modification crucial for the transition from transcription initiation to elongation.

==Role in DNA Repair==
TFIIH's involvement in nucleotide excision repair (NER) highlights its critical role in maintaining genomic integrity. In NER, TFIIH unwinds the DNA around a lesion, such as a thymine dimer caused by UV light, enabling the excision of the damaged strand and subsequent repair. Mutations in TFIIH subunits, particularly in XPB and XPD, are linked to rare genetic disorders like [[Xeroderma Pigmentosum]] and [[Cockayne Syndrome]], which are characterized by sensitivity to UV light and increased risk of skin cancer.

==Cell Cycle Regulation==
The CAK complex of TFIIH also influences the cell cycle by phosphorylating several key proteins, including CDKs (cyclin-dependent kinases), which are vital for cell cycle progression. This regulatory function underscores the importance of TFIIH beyond transcription and DNA repair, highlighting its role in cell proliferation and growth.

==Clinical Significance==
Given its essential functions, TFIIH is a target of interest in the study of cancer and other diseases where transcription, DNA repair, and cell cycle regulation are disrupted. Understanding the mechanisms of TFIIH action and its interactions with other cellular components may lead to novel therapeutic strategies for treating such conditions.

==Research and Future Directions==
Ongoing research aims to elucidate the detailed mechanisms by which TFIIH functions in its various roles and to understand how mutations in TFIIH components contribute to disease. Advances in structural biology techniques, such as cryo-electron microscopy, have provided insights into the architecture of TFIIH and its interactions within the cell, offering potential avenues for drug development.

[[Category:Transcription factors]]
[[Category:DNA repair]]
[[Category:Cell cycle]]

{{Molecular-cell-biology-stub}}
{{Medicine-stub}}

Transcription factor II H - Revision history

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