title: Human cyclin-dependent kinase-activating kinase exists in three distinct complexes.
abstract: Transcription factor IIH (TFIIH) is a multisubunit complex required for transcription and for DNA nucleotide excision repair. TFIIH possesses three enzymatic activities: (i) an ATP-dependent DNA helicase, (ii) a DNA-dependent ATPase, and (iii) a kinase with specificity for the carboxyl-terminal domain of RNA polymerase II. The kinase activity was recently identified as the cdk (cyclin-dependent kinase) activating kinase, CAK, composed of cdk7, cyclin H, and MAT-1. Here we report the isolation and characterization of three distinct CAK-containing complexes from HeLa nuclear extracts: CAK, a novel CAK-ERCC2 complex, and TFIIH. CAK-ERCC2 can efficiently associate with core-TFIIH to reconstitute holo-TFIIH transcription activity. We present evidence proposing a critical role for ERCC2 in mediating the association of CAK with core TFIIH subunits.
authors.affiliation: Howard Hughes Medical Institute, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, 088854-5635, USA.
authors.forename: R
authors.initials: R
authors.lastname: Drapkin
authors.forename: G
authors.initials: G
authors.lastname: Le Roy
authors.forename: H
authors.initials: H
authors.lastname: Cho
authors.forename: S
authors.initials: S
authors.lastname: Akoulitchev
authors.forename: D
authors.initials: D
authors.lastname: Reinberg
mesh_terms: D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism; D019473:Transcription Factors, TFII
chemical_list: D007527:Isoenzymes; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D051758:Transcription Factor TFIIH; D018844:Cyclin-Dependent Kinases