Tripartite DNA Lesion Recognition and Verification by XPC, TFIIH, and XPA in Nucleotide Excision Repair

摘要: Transcription factor IIH (TFIIH) is essential for both transcription and nucleotide excision repair (NER). DNA lesions are initially detected by NER factors XPC XPE or stalled RNA polymerases, but only bulky preferentially repaired NER. To elucidate substrate specificity in NER, we have prepared homogeneous human ten-subunit TFIIH its seven-subunit core (Core7) without the CAK module show that inhibit ATPase helicase activities of XPB XPD Core7 to promote whereas non-genuine substrates no such effect. Moreover, XPA activates unwinding normal Core7, inhibits activity in the presence lesions. Finally, binding thereby enhances XPC-dependent specific recruitment TFIIH. Our results support a tripartite lesion verification mechanism involving XPC, TFIIH, efficient