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

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.

Pubmed ID: 12815074

Authors

  • Ng JM
  • Vermeulen W
  • van der Horst GT
  • Bergink S
  • Sugasawa K
  • Vrieling H
  • Hoeijmakers JH

Journal

Genes & development

Publication Data

July 1, 2003

Associated Grants

None

Mesh Terms

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