Abstract
The human basal transcription factor IIH (TFIIH) is an essential component of the nucleotide excision repair machinery. TFIIH is required for reaction steps concomitant with or prior to the formation of dual incisions in the damaged DNA strand. To understand the mechanism underlying the recruitment of TFIIH to DNA damage sites we have analyzed i) the direct affinity of TFIIH for damaged or undamaged DNA and ii) the interaction of TFIIH with XPA.DNA complexes, formed using unirradiated or UV-irradiated DNA. Filter binding assays showed that TFIIH has some affinity for the DNA, but in contrast to XPA, does not show any preference for UV-irradiated DNA. Pull-down experiments demonstrated that TFIIH binds to XPA.DNA complexes in an UV damage-dependent manner by a direct protein-protein interaction with XPA. We propose that an enhancement of the affinity of XPA protein for TFIIH could arise from conformational changes of XPA when it binds to UV lesions on the DNA.
Highlights
The human basal transcription factor IIH (TFIIH) is an essential component of the nucleotide excision repair machinery
Active processing of DNA damage by nucleotide excision repair (NER) is dependent on the ability to recognize DNA modifications in the genome and on the efficiency with which repair factors are recruited to the site of DNA damage
More specificity in damage recognition may be gained by interaction of XPA with ERCCI (36 –38), which was shown to increase the affinity of XPA for damaged DNA [39]
Summary
The human basal transcription factor IIH (TFIIH) is an essential component of the nucleotide excision repair machinery. TFIIH is thought to be recruited to a promoter, after the formation of the preinitiation complex containing TFIID, TFIIB, TFIIF, and RNA polymerase II on the TATA box consensus sequence [8] Once associated with this complex, TFIIH is likely to function through its ATPdependent helicase subunits, which may facilitate the opening of the promoter region [9] to allow the reading of the DNA. The precise role played by TFIIH during the early reaction steps of NER is not yet certain, but the ATP-dependent helicase activities of the XPB and XPD subunits (26 –29, 6) may facilitate the formation of an open DNA complex, which precedes the formation of dual incisions in the damaged DNA strand [30]
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