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Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair.

The XPC-HR23B complex is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). Its function is unknown. Using a novel DNA damage recognition-competition assay, we identified XPC-HR23B as the earliest damage detector to initiate NER: it acts before the known damage-binding protein XPA. Coimmunoprecipitation and DNase I footprinting show that XPC-HR23B binds to a variety of NER lesions. These results resolve the function of XPC-HR23B, define the first NER stages, and suggest a two-step mechanism of damage recognition involving damage detection by XPC-HR23B followed by damage verification by XPA. This provides a plausible explanation for the extreme damage specificity exhibited by global genome repair. In analogy, in the transcription-coupled NER subpathway, RNA polymerase II may take the role of XPC. After this subpathway-specific initial lesion detection, XPA may function as a common damage verifier and adaptor to the core of the NER apparatus.

Pubmed ID: 9734359

Authors

  • Sugasawa K
  • Ng JM
  • Masutani C
  • Iwai S
  • van der Spek PJ
  • Eker AP
  • Hanaoka F
  • Bootsma D
  • Hoeijmakers JH

Journal

Molecular cell

Publication Data

August 18, 1998

Associated Grants

None

Mesh Terms

  • Base Sequence
  • Binding, Competitive
  • DNA
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins
  • Genome, Human
  • Humans
  • In Vitro Techniques
  • Macromolecular Substances
  • Models, Biological
  • Xeroderma Pigmentosum
  • Xeroderma Pigmentosum Group A Protein