Tbf5 protein domain

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Tbf5
Tbf5
	Crystal structure of the human TFIIH.
Identifiers
Symbol	Tbf5
Pfam	PF06331
InterPro	IPR009400
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Last updated October 29, 2022

In molecular biology, this protein domain represents Tbf5 which stands for TTDA subunit of TFIIH basal transcription factor complex (also known as subunit 5 of RNA polymerase II transcription factor B), and Rex1 a type of nucleotide excision repair (NER) proteins. Nucleotide excision repair is a major pathway for repairing UV light-induced DNA damage in most organisms. The function of this protein is to aid transcription.

Structure

These proteins have a structural motif consisting of a 2-layer sandwich structure with an alpha/beta plait topology.

TFIIH

Transcription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair. The TFIIH complex consists of ten subunits:

ERCC2,
ERCC3,
GTF2H1,
GTF2H2,
GTF2H3,
GTF2H4,
GTF2H5,
MNAT1,
CDK7 and
CCNH.

TTDA is also required for the stability of the TFIIH complex and for the presence of normal levels of TFIIH in the cell. TFIIH is one of five general transcription factors (GTFs) that assemble with RNA polymerase IIat a promoter site prior to the initiation of transcription. It is one of ten subunits that complete part of the 10 subunit protein complex (holoTFIIH) and part of a six-subunit complex of Rad3, Tfb1, Tfb2, Tfb4, Tfb5, and Ssl1 (referred to as core) ^[1]

Function

In humans, the function of Tbf5 is clear, as loss of it leads to trichothiosystropy. Defects in GTF2H5 cause the disease trichothiodystrophy (TTD), therefore GTF2H5 (general transcription factor 2H subunit 5) is also known as the TTD group A (TTDA) subunit (and as Tfb5).^[2] The TTDA subunit is responsible for the DNA repair function of the complex. TTDA is present both bound to TFIIH, and as a free fraction that shuffles between the cytoplasm and nucleus; induction of NER-type DNA lesions shifts the balance towards TTDA's more stable association with TFIIH.^[3]

REX1, which is short for, required for excision 1, is required for DNA repair in the single-celled, photosynthetic algae Chlamydomonas reinhardtii,^[4] and has homologues in other eukaryotes.

Related Research Articles

The preinitiation complex is a complex of approximately 100 proteins that is necessary for the transcription of protein-coding genes in eukaryotes and archaea. The preinitiation complex positions RNA polymerase II at gene transcription start sites, denatures the DNA, and positions the DNA in the RNA polymerase II active site for transcription.

Xeroderma pigmentosum (XP) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused by ultraviolet (UV) light. Symptoms may include a severe sunburn after only a few minutes in the sun, freckling in sun exposed areas, dry skin and changes in skin pigmentation. Nervous system problems, such as hearing loss, poor coordination, loss of intellectual function and seizures, may also occur. Complications include a high risk of skin cancer, with about half having skin cancer by age 10 without preventative efforts, and cataracts. There may be a higher risk of other cancers such as brain cancers.

Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals, radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucleotide excision repair (NER), base excision repair (BER), and DNA mismatch repair (MMR). While the BER pathway can recognize specific non-bulky lesions in DNA, it can correct only damaged bases that are removed by specific glycosylases. Similarly, the MMR pathway only targets mismatched Watson-Crick base pairs.

General transcription factors (GTFs), also known as basal transcriptional factors, are a class of protein transcription factors that bind to specific sites (promoter) on DNA to activate transcription of genetic information from DNA to messenger RNA. GTFs, RNA polymerase, and the mediator constitute the basic transcriptional apparatus that first bind to the promoter, then start transcription. GTFs are also intimately involved in the process of gene regulation, and most are required for life.

XPB is an ATP-dependent DNA helicase in humans that is a part of the TFIIH transcription factor complex.

ERCC2, or XPD is a protein involved in transcription-coupled nucleotide excision repair.

Transcription factor II Human is an important protein complex, having roles in transcription of various protein-coding genes and DNA nucleotide excision repair (NER) pathways. TF_IIH first came to light in 1989 when general transcription factor-δ or basic transcription factor 2 was characterized as an indispensable transcription factor in vitro. This factor was also isolated from yeast and finally named as TF_IIH in 1992.

Transcription factor II E (TF_IIE) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. It is a tetramer of two alpha and two beta chains and interacts with TAF6/TAFII80, ATF7IP, and varicella-zoster virus IE63 protein.

DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ERCC1 gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.

DNA repair protein complementing XP-A cells is a protein that in humans is encoded by the XPA gene.

DNA excision repair protein ERCC-6 is a protein that in humans is encoded by the ERCC6 gene. The ERCC6 gene is located on the long arm of chromosome 10 at position 11.23.

DNA repair protein complementing XP-G cells is a protein that in humans is encoded by the ERCC5 gene.

General transcription factor IIH subunit 4 is a protein that in humans is encoded by the GTF2H4 gene.

DNA excision repair protein ERCC-8 is a protein that in humans is encoded by the ERCC8 gene.

General transcription factor IIH subunit 2 is a protein that in humans is encoded by the GTF2H2 gene.

General transcription factor IIH subunit 1 is a protein that in humans is encoded by the GTF2H1 gene.

General transcription factor IIH subunit 5 is a protein that in humans is encoded by the GTF2H5 gene.

RNA polymerase II holoenzyme is a form of eukaryotic RNA polymerase II that is recruited to the promoters of protein-coding genes in living cells. It consists of RNA polymerase II, a subset of general transcription factors, and regulatory proteins known as SRB proteins.

Trichothiodystrophy (TTD) is an autosomal recessive inherited disorder characterised by brittle hair and intellectual impairment. The word breaks down into tricho – "hair", thio – "sulphur", and dystrophy – "wasting away" or literally "bad nourishment". TTD is associated with a range of symptoms connected with organs of the ectoderm and neuroectoderm. TTD may be subclassified into four syndromes: Approximately half of all patients with trichothiodystrophy have photosensitivity, which divides the classification into syndromes with or without photosensitivity; BIDS and PBIDS, and IBIDS and PIBIDS. Modern covering usage is TTD-P (photosensitive), and TTD.

Progeroid syndromes (PS) are a group of rare genetic disorders that mimic physiological aging, making affected individuals appear to be older than they are. The term progeroid syndrome does not necessarily imply progeria, which is a specific type of progeroid syndrome.

References

↑ Gibbons BJ, Brignole EJ, Azubel M, Murakami K, Voss NR, Bushnell DA, et al. (2012). "Subunit architecture of general transcription factor TFIIH". Proc Natl Acad Sci U S A. 109 (6): 1949–54. Bibcode:2012PNAS..109.1949G. doi: 10.1073/pnas.1105266109 . PMC 3277522 . PMID 22308316.
↑ Giglia-Mari G, Coin F, Ranish JA, Hoogstraten D, Theil A, Wijgers N, Jaspers NG, Raams A, Argentini M, van der Spek PJ, Botta E, Stefanini M, Egly JM, Aebersold R, Hoeijmakers JH, Vermeulen W (July 2004). "A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A". Nat. Genet. 36 (7): 714–9. doi: 10.1038/ng1387 . PMID 15220921.
↑ Giglia-Mari G, Miquel C, Theil AF, Mari PO, Hoogstraten D, Ng JM, Dinant C, Hoeijmakers JH, Vermeulen W (June 2006). "Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells". PLOS Biol. 4 (6): e156. doi:10.1371/journal.pbio.0040156. PMC 1457016 . PMID 16669699.
↑ Cenkci B, Petersen JL, Small GD (June 2003). "REX1, a novel gene required for DNA repair". J. Biol. Chem. 278 (25): 22574–7. doi: 10.1074/jbc.M303249200 . PMID 12697762.

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[pmid22308316-1] Gibbons BJ, Brignole EJ, Azubel M, Murakami K, Voss NR, Bushnell DA, et al. (2012). "Subunit architecture of general transcription factor TFIIH". Proc Natl Acad Sci U S A. 109 (6): 1949–54. Bibcode:2012PNAS..109.1949G. doi: 10.1073/pnas.1105266109 . PMC 3277522 . PMID 22308316.

[pmid15220921-2] Giglia-Mari G, Coin F, Ranish JA, Hoogstraten D, Theil A, Wijgers N, Jaspers NG, Raams A, Argentini M, van der Spek PJ, Botta E, Stefanini M, Egly JM, Aebersold R, Hoeijmakers JH, Vermeulen W (July 2004). "A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A". Nat. Genet. 36 (7): 714–9. doi: 10.1038/ng1387 . PMID 15220921.

[pmid16669699-3] Giglia-Mari G, Miquel C, Theil AF, Mari PO, Hoogstraten D, Ng JM, Dinant C, Hoeijmakers JH, Vermeulen W (June 2006). "Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells". PLOS Biol. 4 (6): e156. doi:10.1371/journal.pbio.0040156. PMC 1457016 . PMID 16669699.

[pmid12697762-4] Cenkci B, Petersen JL, Small GD (June 2003). "REX1, a novel gene required for DNA repair". J. Biol. Chem. 278 (25): 22574–7. doi: 10.1074/jbc.M303249200 . PMID 12697762.

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