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

Kaoru Sugasawa, Jessica M.Y. Ng, Chikahide Masutani, Shigenori Iwai, Peter J. Van Der Spek, André P.M. Eker, Fumio Hanaoka, Dirk Bootsma, Jan H.J. Hoeijmakers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

759 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)223-232
Aantal pagina's10
TijdschriftMolecular Cell
Volume2
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - aug. 1998
Extern gepubliceerdJa

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