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.
| Tbf5 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Crystal structure of the human TFIIH. | |||||||||
| Identifiers | |||||||||
| Symbol | Tbf5 | ||||||||
| Pfam | PF06331 | ||||||||
| InterPro | IPR009400 | ||||||||
| |||||||||
Structure
editThese proteins have a structural motif consisting of a 2-layer sandwich structure with an alpha/beta plait topology.
TFIIH
editTranscription/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
editIn 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.
References
edit- ^ 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.