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

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

K Sugasawa  1 , J M Ng, C Masutani, S Iwai, P J van der Spek, A P Eker, F Hanaoka, D Bootsma, J H Hoeijmakers
Affiliations
Free article

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

K Sugasawa et al. Mol Cell. 1998 Aug.
Free article

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.

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