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 RIS Download
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