From laboratory tests to functional characterisation of Cockayne syndrome

Mech Ageing Dev. May-Jun 2013;134(5-6):171-9. doi: 10.1016/j.mad.2013.03.007. Epub 2013 Apr 6.

Abstract

The significant progress made over the last few years on the pathogenesis of Cockayne syndrome (CS) greatly improved our knowledge on several aspects crucial for development and ageing, demonstrating that this disorder, even if rare, represents a valuable tool to clarify key aspects of human health. Primary cells from patients have been instrumental to elucidate the multiple roles of CS proteins and to approach the dissection of the complex interplay between repair and transcription that is central to the CS clinical phenotype. Here we discuss the results of the cellular assays applied for confirmation of the clinical diagnosis as well as the results of genetic and molecular studies in DNA repair defective patients. Furthermore, we provide a general overview of recent in vivo and in vitro studies indicating that both CSA and CSB proteins are involved in distinct aspects of the cellular responses to UV and oxidative stress, transcription and regulation of gene expression, chromatin remodelling, redox balance and cellular bioenergetics. In light of the literature data, we will finally discuss how inactivation of specific functional roles of CS proteins may differentially affect the phenotype, thus explaining the wide range in type and severity of symptoms reported in CS patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromatin Assembly and Disassembly / genetics*
  • Chromatin Assembly and Disassembly / radiation effects
  • Cockayne Syndrome* / genetics
  • Cockayne Syndrome* / metabolism
  • Cockayne Syndrome* / pathology
  • DNA Helicases* / biosynthesis
  • DNA Helicases* / genetics
  • DNA Repair Enzymes* / biosynthesis
  • DNA Repair Enzymes* / genetics
  • DNA Repair*
  • Humans
  • Oxidative Stress / genetics
  • Oxidative Stress / radiation effects
  • Poly-ADP-Ribose Binding Proteins
  • Transcription Factors* / biosynthesis
  • Transcription Factors* / genetics
  • Transcription, Genetic / genetics*
  • Transcription, Genetic / radiation effects
  • Ultraviolet Rays / adverse effects

Substances

  • ERCC8 protein, human
  • Poly-ADP-Ribose Binding Proteins
  • Transcription Factors
  • DNA Helicases
  • ERCC6 protein, human
  • DNA Repair Enzymes