Relevance of the extracellular matrix in the puzzling genotype-phenotype relationships of XPD mutations (Comunicazione a convegno)

Type
Label
  • Relevance of the extracellular matrix in the puzzling genotype-phenotype relationships of XPD mutations (Comunicazione a convegno) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Alternative label
  • Orioli D (2014)
    Relevance of the extracellular matrix in the puzzling genotype-phenotype relationships of XPD mutations
    in International Symposium on Xeroderma Pigmentosum and Felated Diseases: Disorders of DNA Damage Response-Bench to Bedside, Kobe, Japan, 5-7 Marzo 2014
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Orioli D (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Orioli D: IGM CNR, Pavia Italy (literal)
Titolo
  • Relevance of the extracellular matrix in the puzzling genotype-phenotype relationships of XPD mutations (literal)
Abstract
  • XPD is a subunit of TFIIH, a multi-protein complex involved in basal transcription, gene expression regulation and nucleotide excision repair (NER), the main pathway responsible for the removal of UV-induced DNA lesions. The engagement of TFIIH in distinct cellular processes has provided a rationale for explaining the variety of clinical entities resulting from mutations in XPD. The most common of these disorders, namely xeroderma pigmentosum (XP) and trichothiodystrophy (TTD), share only cutaneous photosensitivity and represent a valuable model system for elucidating molecular processes relevant for carcinogenesis (XP) or developmental alterations and ageing (TTD). By gene expression profiling, we have identified TFIIH-dependent transcriptional impairments affecting the expression of specific sets of genes related to the extracellular matrix (ECM). These transcriptional deregulations are specific for TTD primary fibroblasts and result in structural alterations as well as metabolic disturbances of the ECM in both in vitro TTD cell cultures and skin tissue. The ECM is a complex network of macromolecules that provide not only a structural support to cells and tissues but also elicit signalling events controlling cell behaviour and tissue homeostasis. Indeed, the ECM alterations affecting TTD dermal fibroblasts impair some of their cellular features, among which migration and wound healing, which can be fully recovered by inhibiting the activity of specific ECM molecules. The ECM functional relevance in the modulation of cellular events such as cell adhesion, proliferation, differentiation and survival, points to the involvement of ECM alterations in the phenotypic differences between TTD and XP patients (literal)
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