CORRECTION OF XERODERMA-PIGMENTOSUM REPAIR DEFECT BY BASAL TRANSCRIPTION FACTOR BTF2 (TFIIH)

ERCC3 was initially identified as a gene correcting the nucleotide exc ision repair (NER) defect of xeroderma pigmentosum complementation gro up B (XP-B). The recent finding that its gene product is identical to the p89 subunit of basal transcription factor BTF2(TFIIH), opened the possibility that it is not directly involved in NER but that it regula tes the transcription of one or more NER genes. Using an in vivo micro injection repair assay and an in vitro NER system based on cell-free e xtracts we demonstrate that ERCC3 in BTF2 is directly implicated in ex cision repair. Antibody depletion experiments support the idea that th e p62 BTF2 subunit and perhaps the entire transcription factor functio nin NER. Microinjection experiments suggest that exogenous ERCC3 can e xchange with ERCC3 subunits in the complex. Expression of a dominant n egative K436 - RERCC3 mutant, expected to have lost all helicase activ ity, completely abrogates NER and transcription and concomitantly indu ces a dramatic chromatin collapse. These findings establish the role o f ERCC3 and probably the entire BTF2 complex in transcription in vivo which was hitherto only demonstrated in vitro. The results strongly su ggest that transcription itself is a critical componentfor maintenance of chromatin structure. The remarkable dual role of ERCC3 in NER and transcription provides a clue in understanding the complex clinical fe atures of some inherited repair syndromes