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...

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Veröffentlicht in:Molecular cell 1998-08, Vol.2 (2), p.223-232
Hauptverfasser: Sugasawa, Kaoru, Ng, Jessica M.Y, Masutani, Chikahide, Iwai, Shigenori, van der Spek, Peter J, Eker, André P.M, Hanaoka, Fumio, Bootsma, Dirk, Hoeijmakers, Jan H.J
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Sprache:eng
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Zusammenfassung: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.
ISSN:1097-2765
1097-4164
1097-4164
DOI:10.1016/S1097-2765(00)80132-X