The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor.

Schaeffer, Laurent; Moncollin, Vincent; Roy, Richard; Staub, Adrien; Mezzina, Mauro; Sarasin, Alain; Weeda, Geert; Hoeijmakers, Jan H.J.; Egly, Jean‐Marc

doi:10.1002/j.1460-2075.1994.tb06522.x

Cited by 353 publications

(232 citation statements)

References 24 publications

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“…Consistent with this, TFIIH has an associated ATP-dependent DNA helicase activity (95,96). In particular, the yeast TFIIH subunit RAD3 (22) and its human counterpart XPD (ERCC2) (94) are DNA helicases (19,106). Moreover, human XPB (ERCC3) is a helicase (19,95), and XPB and its yeast homolog, SSL2, have helicase motifs in their amino acid sequences (33,75,113).…”

Section: Discussionmentioning

confidence: 99%

Binding of basal transcription factor TFIIH to the acidic activation domains of VP16 and p53.

Xiao¹,

Pearson²,

Coulombe³

et al. 1994

Mol. Cell. Biol.

339

274

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Acidic transcriptional activation domains function well in both yeast and mammalian cells, and some have been shown to bind the general transcription factors TFIID and TFIIB. We now show that two acidic transactivators, herpes simplex virus VP16 and human p53, directly interact with the multisubunit human general transcription factor TFIHH and its Saccharomyces cerevisuze counterpart, factor b. The VP16-and p53-binding domains in these factors lie in the p62 subunit of TFIIH and in the homologous subunit, TFB1, of factor b. Point mutations in VP16 that reduce its transactivation activity in both yeast and mammalian cells weaken its binding to both yeast and human TFIIH. This suggests that binding of activation domains to TFIIH is an important aspect of transcriptional activation.Accurate transcription in vitro by human RNA polymerase II involves the general transcription factors TFIIA, TFIIB, TFIID, TFIIE, TFIIF (RAP30 and RAP74), TFIIH (also known as BTF2), and TFIIJ (reviewed in references 13 and 121). Beginning with TFIID, which recognizes the TATA boxes present in many promoters for RNA polymerase II, these factors and RNA polymerase II can be assembled in a defined order onto a promoter (5). TFIIH and TFIIJ are the last of these factors to bind to an assembling initiation complex (12,14,26), and TFIIH, also known as BTF2, is the only factor known to possess associated enzymatic activities. These include an ATP-dependent DNA helicase activity (95, 96) and a protein kinase activity that can phosphorylate the carboxyterminal heptapeptide repeat domain (CTD) of the largest subunit of RNA polymerase 11 (12, 21,68 herpes simplex virus transactivator VP16 (107) and in the N-terminal 73 amino acids of the mammalian tumor suppressor protein p53 (23). The p53 protein has a site-specific DNA-binding domain in its carboxy-terminal portion (101). VP16 does not, by itself, bind specifically to DNA, but instead its amino-terminal portion binds DNA in association with mammalian factors, including the POU homeodomain protein Oct-1 that recognizes octamer sequences in DNA (28,60,102). When fused to the DNA-binding domain of GAL4, the VP16 and p53 activation domains stimulate transcription in yeast and human cells of a gene bearing GAL4-binding sites (9,16,23,74,87,92). These observations imply that common mechanisms for transcriptional activation by acidic activators may exist in fungi and mammals.Many activation domains have been shown to interact with the TATA-box-binding protein (TBP) subunit of TFIID. These include the highly acidic activation domains in VP16 (50,103), p53 (10,67,72,84,97,108),118), and E2F-1 (37), as well as other kinds of activation domains found in the adenovirus activator ElA (48, 62), the Epstein-Barr virus proteins Zta (64) and R (70), the human T-cell leukemia virus type 1 (HTLV-1) activator Taxl (8), the transactivator Tat of human immunodeficiency virus type 1 (HIV-1) (53), and human c-Fos and c-Jun (85), PU-1 (38), and Spl (20). In certain cases, reduced binding of TBP by activation domains wit...

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Section: Discussionmentioning

confidence: 99%

Binding of basal transcription factor TFIIH to the acidic activation domains of VP16 and p53.

Xiao¹,

Pearson²,

Coulombe³

et al. 1994

Mol. Cell. Biol.

339

274

View full text Add to dashboard Cite

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“…Yeast TFIIH can be dissociated into a core complex, which includes both ATPase/helicases, and a kinase complex, comprising the kinase and cyclin subunits, termed TFIIK (2). While the ATPase/helicases were the first components of TFIIH shown to be involved in DNA damage repair (3,4), additional subunits of the core complex prove to be required for repair as well (5)(6)(7)(8)(9). The human counterpart of TFIIK, known as CAK, was originally identified on the basis of its capacity to activate cyclindependent kinases involved in cell cycle control through phosphorylation of a key threonine residue in vitro (10,11).…”

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confidence: 99%

Genes For Tfb2, Tfb3, and Tfb4 Subunits of Yeast Transcription/Repair Factor IIH

Feaver

Henry

Wang

et al. 1997

Journal of Biological Chemistry

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Genes for the Tfb2, Tfb3, and Tfb4 subunits of yeast RNA polymerase transcription factor IIH (TFIIH) are described. All three genes are essential for cell viability, and antibodies against Tfb3 specifically inhibit transcription in vitro. A C-terminal deletion of Tfb2 caused a defect in nucleotide excision repair, as shown by UV sensitivity of the mutant strain and loss of nucleotide excision repair activity in cell extracts (restored by the addition of purified TFIIH). An interaction between Tfb3 and the Kin28 subunit of TFIIH was detected by the two-hybrid approach, consistent with a role for Tfb3 in linking kinase and core domains of the factor. The deduced amino acid sequence of Tfb2 is similar to that of the 52-kDa subunit of human TFIIH, while Tfb3 is identified as a RING finger protein homologous to the 36-kDa subunit of murine CAK (cyclin-dependent kinase activating kinase) and to the 32-kDa subunit of human TFIIH. Tfb4 is homologous to p34 of human TFIIH and is identified as the weakly associated 37-kDa subunit of the yeast factor. These and other findings reveal a oneto-one correspondence and high degree of sequence similarity between the entire set of yeast and human TFIIH polypeptides.

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“…The first four subunits have been identified as the products of the SSL2 (RAD25), RAD3, TFB1, and SSL1 genes, respectively (6,10,22). Homologous genes designated XPB, XPD, p62, and p44, respectively, encode subunits of TFIIH(BTF2) in human cells (4,7,13,19,20). Mutations in the XPB and XPD genes are associated with several human hereditary diseases, including xeroderma pigmentosum, xeroderma pigmentosum with Cockayne's syndrome, and trichothiodystrophy (1, 27).…”

mentioning

confidence: 99%

The Yeast TFB1 and SSL1 Genes, Which Encode Subunits of Transcription Factor IIH, Are Required for Nucleotide Excision Repair and RNA Polymerase II Transcription

Wang

Buratowski

Svejstrup

et al. 1995

Molecular and Cellular Biology

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The essential TFB1 and SSL1 genes of the yeast Saccharomyces cerevisiae encode two subunits of the RNA polymerase II transcription factor TFIIH (factor b). Here we show that extracts of temperature-sensitive mutants carrying mutations in both genes (tfb1-101 and ssl1-1) are defective in nucleotide excision repair (NER) and RNA polymerase II transcription but are proficient for base excision repair. RNA polymerase II-dependent transcription at the CYC1 promoter was normal at permissive temperatures but defective in extracts preincubated at a restrictive temperature. In contrast, defective NER was observed at temperatures that are permissive for growth. Additionally, both mutants manifested increased sensitivity to UV radiation at permissive temperatures. The extent of this sensitivity was not increased in a tfb1-101 strain and was only slightly increased in a ssl1-1 strain at temperatures that are semipermissive for growth. Purified factor TFIIH complemented defective NER in both tfb1-101 and ssl1-1 mutant extracts. These results define TFB1 and SSL1 as bona fide NER genes and indicate that, as is the case with the yeast Rad3 and Ssl2 (Rad25) proteins, Tfb1 and Ssl1 are required for both RNA polymerase II basal transcription and NER. Our results also suggest that the repair and transcription functions of Tfb1 and Ssl1 are separable.Transcription from mammalian or Saccharomyces cerevisiae promoters by RNA polymerase II requires multiple initiation factors, including TFIIB (factor e), TFIID (factor d), TFIIE (factor a), TFIIF (factor g), and TFIIH (factor b) (2, 6). The transcriptionally active form of factor b in a yeast reconstituted system in vitro is designated holo-TFIIH, comprising core TFIIH, Ssl2 protein, and the three-subunit kinase TFIIK (22). Core TFIIH with associated Ssl2 (core TFIIH-Ssl2) consists of six subunits of ϳ105, 85, 70, 50, 55, and 38 kDa (6,22). The first four subunits have been identified as the products of the SSL2 (RAD25), RAD3, TFB1, and SSL1 genes, respectively (6,10,22). Homologous genes designated XPB, XPD, p62, and p44, respectively, encode subunits of TFIIH(BTF2) in human cells (4,7,13,19,20). Mutations in the XPB and XPD genes are associated with several human hereditary diseases, including xeroderma pigmentosum, xeroderma pigmentosum with Cockayne's syndrome, and trichothiodystrophy (1, 27).Core TFIIH-Ssl2 is required for both transcription by RNA polymerase II and nucleotide excision repair (NER) in S. cerevisiae and humans (4,23,25,28). Consistent with their requirement for transcription, SSL2, RAD3, TFB1, and SSL1 are essential yeast genes (10-12, 17, 18, 34). The same presumably holds true for the homologous human genes, though the essentiality of gene function is difficult to demonstrate directly for mammalian cells.Recent studies have shown that cell extracts of viable yeast rad3 and ssl2 mutants are defective in NER (28). These defects can be corrected by complementation of the extracts with purified core TFIIH or core TFIIH-Ssl2 complexes, respectively, but not by complem...

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The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor.

Cited by 353 publications

References 24 publications

Binding of basal transcription factor TFIIH to the acidic activation domains of VP16 and p53.

Binding of basal transcription factor TFIIH to the acidic activation domains of VP16 and p53.

Genes For Tfb2, Tfb3, and Tfb4 Subunits of Yeast Transcription/Repair Factor IIH

The Yeast TFB1 and SSL1 Genes, Which Encode Subunits of Transcription Factor IIH, Are Required for Nucleotide Excision Repair and RNA Polymerase II Transcription

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