Xeroderma Pigmentosum Group C Protein Complex Is the Initiator of Global Genome Nucleotide Excision Repair

Mol Cell. 1998 Aug;2(2):223-32. doi: 10.1016/s1097-2765(00)80132-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • DNA-Binding Proteins
  • Macromolecular Substances
  • XPA protein, human
  • Xeroderma Pigmentosum Group A Protein
  • XPC protein, human
  • DNA