Interacting partners of the Tfb2 subunit from yeast TFIIH.
TFIIH is an evolutionary conserved eukaryotic multi-protein complex composed of ten subunits. It is involved in transcription, cell cycle regulation, RNA splicing and the nucleotide excision DNA repair pathway (NER). Depending on the process in which it is functioning, the composition of TFIIH varies and activities of its subunits are differentially regulated. Here we focused on interplay between the Ssl2, Tfb2 and Tfb5 subunits of TFIIH from Saccharomyces cerevisiae. We found that Tfb2 bridges the Ssl2 helicase and the NER-specific Tfb5 subunit. Moreover, the Tfb5-interacting domain of Tfb2 also binds nucleic acids (NA), although the addition of Tfb5 triggers dissociation of NA from Tfb2. In yeast cells, deletion of TFB5 is more detrimental to NER than loss of the Tfb5/NA-interacting domain of Tfb2, while combining these mutations resulted in suppression of the UV sensitivity of tfb5Delta. The implications of our findings in regards to TFIIH function and group A trichothiodystrophy, an inherited disease associated with mutations in the human TFB5 gene, are discussed.
Kainov
Denis E
DE
Institute for Molecular Medicine Finland, University of Helsinki, Finland.
Selth
Luke A
LA
Svejstrup
Jesper Q
JQ
Egly
Jean-Marc
JM
Poterzsman
Arnaud
A
D000595:Amino Acid Sequence; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004271:DNA, Fungal / Q000737:chemistry / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051758:Transcription Factor TFIIH / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D004271:DNA, Fungal; D021122:Protein Subunits; C489575:SSL2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C517875:Tfb2 protein, S cerevisiae; C517874:Tfb5 protein, S cerevisiae; D051758:Transcription Factor TFIIH; D004265:DNA Helicases