The general transcription-repair factor TFIIH is recruited to the excision repair complex by the XPA protein independent of the TFIIE transcription factor.
Recent studies have revealed that the general transcription factor TFIIH is also a general excision repair factor which, along with several other proteins, is required for transcription-independent excision reaction. As a general transcription factor, TFIIH is recruited to RNA polymerase II-promoter complex by another general transcription factor called TFIIE. We were interested in knowing whether TFIIE is also involved in recruiting TFIIH to the excision repair complex. We found that cell-free extract depleted of TFIIE carried out excision repair at a normal rate, leading us to conclude that TFIIE is not involved in recruiting TFIIH to the damage site and has no role in general excision repair. In contrast, the human damage recognition protein XPA specifically binds to TFIIH and apparently recruits it to the damage site. The carboxyl-terminal half of XPA is responsible for specific interaction with TFIIH. The C261S/C264S mutant of XPA bound the ERCC1-XPF complex normally, but failed to bind TFIIH and failed to complement an XP-A mutant cell-free extract indicating that the XPA-TFIIH interaction is essential to effecting the excision reaction. Interestingly, XPA also binds to the p34 subunit of TFIIE specifically and in competition with the p56 subunit of TFIIE. This latter interaction has no apparent role in general excision repair but may be relevant in the transcription-coupled repair reaction.
Park
C H
CH
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599.
Mu
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Reardon
J T
JT
Sancar
A
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D002474:Cell-Free System; D004265:DNA Helicases / Q000378:metabolism*; D017931:DNA Primers; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism*; D019473:Transcription Factors, TFII; D051760:Xeroderma Pigmentosum Group A Protein
D017931:DNA Primers; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D019473:Transcription Factors, TFII; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C066644:transcription factor TFIIE; D051758:Transcription Factor TFIIH; D004265:DNA Helicases