1998-08-01
Xeroderma pigmentosum group C complex is the initiator of global genome repair.
Publication
Publication
Molecular Cell , Volume 2 - Issue 2 p. 223- 232
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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Elsevier | |
doi.org/10.1016/S1097-2765(00)80132-X, hdl.handle.net/1765/3139 | |
Molecular Cell | |
Organisation | Erasmus MC: University Medical Center Rotterdam |
Sugasawa, K., Ng, J., Masutani, C., van der Spek, P., Eker, A., Hanaoka, F., … Hoeijmakers, 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 |