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.

Additional Metadata
Keywords *DNA Repair, 0 (DNA-Binding Proteins), 0 (Macromolecular Systems), 0 (xeroderma pigmentosum group A complementing protein), 156533-34-5 (XPCC protein, human), 9007-49-2 (dna), Base Sequence, Binding, Competitive, DNA Damage, DNA-Binding Proteins/chemistry/*genetics/*metabolism, DNA/genetics/metabolism, Genome, Human, Human, In Vitro, Macromolecular Systems, Models, Biological, Support, Non-U.S. Gov't, Xeroderma Pigmentosum/genetics/metabolism
Publisher Elsevier
Persistent URL dx.doi.org/10.1016/S1097-2765(00)80132-X, hdl.handle.net/1765/3139
Journal Molecular Cell
Citation
Sugasawa, K, Ng, J.M.Y, Masutani, C, van der Spek, P.J, Eker, A.P.M, Hanaoka, F, … Hoeijmakers, J.H.J. (1998). Xeroderma pigmentosum group C complex is the initiator of global genome repair. Molecular Cell, 2(2), 223–232. doi:10.1016/S1097-2765(00)80132-X