Reduced amounts of collagen type VI reveal extracellular matrix defects in trichothiodystrophy and a new role of TFIIH in transcription derepression (Contributo in atti di convegno)

Type
Label
  • Reduced amounts of collagen type VI reveal extracellular matrix defects in trichothiodystrophy and a new role of TFIIH in transcription derepression (Contributo in atti di convegno) (literal)
Anno
  • 2011-01-01T00:00:00+01:00 (literal)
Alternative label
  • Orioli D, Nardo T, Mura M, Botta E, Compe E, Egly JM, Peverali AF and Stefanini M (2011)
    Reduced amounts of collagen type VI reveal extracellular matrix defects in trichothiodystrophy and a new role of TFIIH in transcription derepression
    in Conference on Responses to DNA damage: from molecular mechanism to human disease, Egmond aan Zee, The Netherlands, 3-8 Aprile 2011
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Orioli D, Nardo T, Mura M, Botta E, Compe E, Egly JM, Peverali AF and Stefanini M (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Orioli D, Nardo T, Mura M, Botta E, Peverali AF and Stefanini M: IGM CNR, Pavia Italy Compe E and Egly JM: IGBMC CNRS, Strasbourg France (literal)
Titolo
  • Reduced amounts of collagen type VI reveal extracellular matrix defects in trichothiodystrophy and a new role of TFIIH in transcription derepression (literal)
Abstract
  • Patients affected by the photosensitive form of trichothiodystrophy (TTD) are mutated in one of three genes (XPB, XPD and GTF2H5/TTDA) that encode distinct subunits of the transcription/DNA repair factor TFIIH. As a consequence, these patients show an altered cellular response to ultraviolet (UV) light due to defects in nucleotide excision repair (NER), the sole mechanism that in human cells removes UV-induced DNA damage. Moreover, all the mutations responsible for TTD cause a decrease by up to 70% in the cellular content of TFIIH and interfere with the transcriptional activity of TFIIH. Emerging evidence supports the hypothesis that the reduced amount of mutated TFIIH may become limiting in TTD terminally differentiated tissues, thus being insufficient to guarantee adequate transcriptional activity of highly expressed genes. In view of the skin defects typically present in TTD patients, we searched for possible alterations in the extracellular matrix (ECM), the structure synthesized mainly by dermal fibroblasts that forms the bulk of the dermis and plays fundamental roles in normal tissue homeostasis, cell adhesion and cell migration. We have obtained the first evidence that mutations in XPD associated with TTD cause a reduced content of the collagen type VI alpha 1 subunit (COL6A1), a fundamental component of the soft connective tissues involved in cell-matrix communications. The reduction is due to a severe impairment in the promoter activity of COL6A1 that fails to up-regulate its expression in TTD primary fibroblasts in response to confluence. By disclosing the mechanism of COL6A1 transcription regulation in primary human fibroblasts, we have highlighted a new role of TFIIH in transcription derepression. As well as identifying a new marker for TTD diagnosis, these findings contribute to understand the aetiology of those symptoms that TTD shares with the hereditary disorders due to mutations in COL6A1. (literal)
Prodotto di
Autore CNR

Incoming links:


Prodotto
Autore CNR di
data.CNR.it