Selective Regulation of Vitamin D Receptor-Responsive Genes by TFIIH

Drané, Pascal; Compe, Emmanuel; Catez, Philippe; Chymkowitch, Pierre; Egly, Jean‐Marc

doi:10.1016/j.molcel.2004.10.007

Cited by 68 publications

(53 citation statements)

References 47 publications

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“…The recent discovered differential phosphorylation of the XPB subunit of TFIIH after UV [48], suggests an active switch between the function of TFIIH in repair and transcription. Recently, the multifunctionality of TFIIH has been complemented with documented involvements in activated RNA polymerase II transcription [49] and [50], in basal transcription initiation of rRNA genes by RNA polymerase I [51] and [52] and a possible role of the CAK subcomplex in cell cycle [47] and [53]. The ERCC1/XPF complex is a NER factor with engagements in interstrand cross-link repair, since deficiency for this structure-specific endonuclease causes sensitivity for cross-linking agents.…”

Section: Involvement Of Ner Factors In Other (Dna Repair) Processesmentioning

confidence: 99%

Tissue specific mutagenic and carcinogenic responses in NER defective mouse models

Wijnhoven

Hoogervorst

Waard

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Several mouse models with defects in genes encoding components of the nucleotide excision repair (NER) pathway have been developed. In NER two different sub-pathways are known, i.e. transcription-coupled repair (TC-NER) and global-genome repair (GG-NER). A defect in one particular NER protein can lead to a (partial) defect in GG-NER, TC-NER or both. GG-NER defects in mice predispose to cancer, both spontaneous as well as UV-induced. As such these models (Xpa, Xpc and Xpe) recapitulate the human xeroderma pigmentosum (XP) syndrome. Defects in TC-NER in humans are associated with Cockayne syndrome (CS), a disease not linked to tumor development. Mice with TC-NER defects (Csa and Csb) areexcept for the skin -not susceptible to develop (carcinogen-induced) tumors. Some NER factors, i.e. XPB, XPD, XPF, XPG and ERCC1 have functions outside NER, like transcription initiation and inter-strand crosslink repair. Deficiencies in these processes in mice lead to very severe phenotypes, like trichothiodystrophy (TTD) or a combination of XP and CS. In most cases these animals have a (very) short life span, display segmental progeria, but do not develop tumors. Here we will overview the available NER-related mouse models and will discuss their phenotypes in terms of (chemical-induced) tissue-specific tumor development, mutagenesis and premature aging features.

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Section: Involvement Of Ner Factors In Other (Dna Repair) Processesmentioning

confidence: 99%

Tissue specific mutagenic and carcinogenic responses in NER defective mouse models

Wijnhoven

Hoogervorst

Waard

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…All of the mutations associated with TTD result in reduced cellular levels (8,9) and impaired functioning of TFIIH in NER and basal transcription (10)(11)(12). Furthermore, they may interfere with the role of TFIIH in transcription regulation (13)(14)(15)(16).…”

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confidence: 99%

TFIIH-dependent MMP-1 overexpression in trichothiodystrophy leads to extracellular matrix alterations in patient skin

Arseni

Lanzafame

Compe

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Mutations in the XPD subunit of the DNA repair/transcription factor TFIIH result in distinct clinical entities, including the cancerprone xeroderma pigmentosum (XP) and the multisystem disorder trichothiodystrophy (TTD), which share only cutaneous photosensitivity. Gene-expression profiles of primary dermal fibroblasts revealed overexpression of matrix metalloproteinase 1 (MMP-1), the gene encoding the metalloproteinase that degrades the interstitial collagens of the extracellular matrix (ECM), in TTD patients mutated in XPD compared with their healthy parents. The defect is observed in TTD and not in XP and is specific for fibroblasts, which are the main producers of dermal ECM. MMP-1 transcriptional up-regulation in TTD is caused by an erroneous signaling mediated by retinoic acid receptors on the MMP-1 promoter and leads to hypersecretion of active MMP-1 enzyme and degradation of collagen type I in the ECM of cell/tissue systems and TTD patient skin. In agreement with the well-known role of ECM in eliciting signaling events controlling cell behavior and tissue homeostasis, ECM alterations in TTD were shown to impact on the migration and wound-healing properties of patient dermal fibroblasts. The presence of a specific inhibitor of MMP activity was sufficient to restore normal cell migration, thus providing a potential approach for therapeutic strategies. This study highlights the relevance of ECM anomalies in TTD pathogenesis and in the phenotypic differences between TTD and XP.T he extracellular matrix (ECM) is a complex structural network that surrounds and supports cells within connective tissues. It generally includes three major types of macromolecules: fibrous proteins (collagens and elastic fibers), glycoproteins (such as fibronectins and laminins), and glycosaminoglycans/ proteoglycans. The type, amount and composition of the ECM give tissues their unique physical and biological properties (1). Notably, the ECM is not only a structural scaffold but also exhibits important functional roles in controlling key cellular events (e.g., adhesion, migration, proliferation, differentiation, and survival) involved in tissue homeostasis, development, inflammation, and tissue repair (2, 3). Thus, inherited or acquired structural alterations as well as metabolic disturbances of the ECM may cause cellular and tissue changes leading to the onset and progression of specific disorders, such as those affecting the connective tissues (osteogenesis imperfecta, Ehlers-Danlos syndrome, and Marfan's syndrome) or demanding ECM degradation (tumor invasion and metastasis) (4, 5). Recently, a reduced synthesis of the ECM component collagen type VI (COL6) was shown in confluent fibroblast cultures from patients with trichothiodystrophy [TTD; Online Mendelian Inheritance in Man (OMIM) #601675] (6), an autosomal recessive disorder characterized by symptoms affecting several tissues and organs (7). The most relevant features of TTD are hair abnormalities, ichthyotic skin, physical and mental retardation, neurodegeneration, and sign...

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“…Furthermore, XPG was recently identified as a protein required for maintaining the integrity of the TFIIH complex, and therefore also engaged in the transcription process (20). Even though the contribution of the DNA repair deficiency to the clinical features of patients with XP, CS, or XP/ CS is irrefutable, studies have shown a clear dysregulation of a variety of transcriptional pathways, which may also contribute to the clinical phenotype of these patients (21)(22)(23)(24)(25)(26)(27). Interestingly, at the cellular level, XP/CS cells share with CS cells a sustained global transcriptional arrest after UV irradiation, which has been always explained by the inability of these cells to perform TCR (17,28).…”

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confidence: 99%

Sirt1 suppresses RNA synthesis after UV irradiation in combined xeroderma pigmentosum group D/Cockayne syndrome (XP-D/CS) cells

Vélez-Cruz

Zadorin

Coin

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Specific mutations in the XPD subunit of transcription factor IIH result in combined xeroderma pigmentosum (XP)/Cockayne syndrome (CS), a severe DNA repair disorder characterized at the cellular level by a transcriptional arrest following UV irradiation. This transcriptional arrest has always been thought to be the result of faulty transcription-coupled repair. In the present study, we showed that, following UV irradiation, XP-D/CS cells displayed a gross transcriptional dysregulation compared with "pure" XP-D cells or WT cells. Furthermore, global RNA-sequencing analysis showed that XP-D/CS cells repressed the majority of genes after UV, whereas pure XP-D cells did not. By using housekeeping genes as a model, we demonstrated that XP-D/CS cells were unable to reassemble these gene promoters and thus to restart transcription after UV irradiation. Furthermore, we found that the repression of these promoters in XP-D/CS cells was not a simple consequence of deficient repair but rather an active heterochromatinization process mediated by the histone deacetylase Sirt1. Indeed, RNA-sequencing analysis showed that inhibition of and/or silencing of Sirt1 changed the chromatin environment at these promoters and restored the transcription of a large portion of the repressed genes in XP-D/CS cells after UV irradiation. Our work demonstrates that a significant part of the transcriptional arrest displayed by XP-D/CS cells arises as a result of an active repression process and not simply as a result of a DNA repair deficiency. This dysregulation of Sirt1 function that results in transcriptional repression may be the cause of various severe clinical features in patients with XP-D/ CS that cannot be explained by a DNA repair defect.nucleotide excision repair | sirtuins | aging | progeria

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Selective Regulation of Vitamin D Receptor-Responsive Genes by TFIIH

Cited by 68 publications

References 47 publications

Tissue specific mutagenic and carcinogenic responses in NER defective mouse models

Tissue specific mutagenic and carcinogenic responses in NER defective mouse models

TFIIH-dependent MMP-1 overexpression in trichothiodystrophy leads to extracellular matrix alterations in patient skin

Sirt1 suppresses RNA synthesis after UV irradiation in combined xeroderma pigmentosum group D/Cockayne syndrome (XP-D/CS) cells

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