A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein

Genes Dev. 2003 Jul 1;17(13):1630-45. doi: 10.1101/gad.260003. Epub 2003 Jun 18.


Primary DNA damage sensing in mammalian global genome nucleotide excision repair (GG-NER) is performed by the xeroderma pigmentosum group C (XPC)/HR23B protein complex. HR23B and HR23A are human homologs of the yeast ubiquitin-domain repair factor RAD23, the function of which is unknown. Knockout mice revealed that mHR23A and mHR23B have a fully redundant role in NER, and a partially redundant function in embryonic development. Inactivation of both genes causes embryonic lethality, but appeared still compatible with cellular viability. Analysis of mHR23A/B double-mutant cells showed that HR23 proteins function in NER by governing XPC stability via partial protection against proteasomal degradation. Interestingly, NER-type DNA damage further stabilizes XPC and thereby enhances repair. These findings resolve the primary function of RAD23 in repair and reveal a novel DNA-damage-dependent regulation mechanism of DNA repair in eukaryotes, which may be part of a more global damage-response circuitry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetoxyacetylaminofluorene / pharmacology
  • Animals
  • Cell Line
  • Cysteine Endopeptidases / metabolism
  • DNA Damage*
  • DNA Repair Enzymes
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Targeting
  • Hot Temperature
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multienzyme Complexes / metabolism
  • Proteasome Endopeptidase Complex
  • Recombinant Fusion Proteins / metabolism
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / radiation effects
  • Transfection
  • Ubiquitin / metabolism
  • Ultraviolet Rays


  • DNA-Binding Proteins
  • Multienzyme Complexes
  • RAD23B protein, human
  • Rad23a protein, mouse
  • Rad23b protein, mouse
  • Recombinant Fusion Proteins
  • Ubiquitin
  • Xpc protein, mouse
  • RAD23A protein, human
  • XPC protein, human
  • Acetoxyacetylaminofluorene
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • DNA Repair Enzymes