Detecting UV-lesions in the genome: The modular CRL4 ubiquitin ligase does it best!

FEBS Lett. 2011 Sep 16;585(18):2818-25. doi: 10.1016/j.febslet.2011.04.064. Epub 2011 May 6.

Abstract

The DDB1-DDB2-CUL4-RBX1 complex serves as the primary detection device for UV-induced lesions in the genome. It simultaneously functions as a CUL4 type E3 ubiquitin ligase. We review the current understanding of this dual function ubiquitin ligase and damage detection complex. The DDB2 damage binding module is merely one of a large family of possible DDB1-CUL4 associated factors (DCAF), most of which are substrate receptors for other DDB1-CUL4 complexes. DDB2 and the Cockayne-syndrome A protein (CSA) function in nucleotide excision repair, whereas the remaining receptors operate in a wide range of other biological pathways. We will examine the modular architecture of DDB1-CUL4 in complex with DDB2, CSA and CDT2 focusing on shared architectural, targeting and regulatory principles.

Publication types

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

MeSH terms

  • Cullin Proteins / metabolism
  • DNA Damage*
  • DNA Repair Enzymes / metabolism
  • DNA Repair*
  • DNA-Binding Proteins / metabolism
  • Genome, Human / genetics
  • Genome, Human / radiation effects*
  • Humans
  • Models, Genetic
  • Nuclear Proteins / metabolism
  • Transcription Factors / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Ultraviolet Rays*

Substances

  • CUL4A protein, human
  • Cullin Proteins
  • DDB1 protein, human
  • DDB2 protein, human
  • DNA-Binding Proteins
  • DTL protein, human
  • ERCC8 protein, human
  • Nuclear Proteins
  • Transcription Factors
  • Ubiquitin-Protein Ligases
  • DNA Repair Enzymes