HUMAN CYCLIN-DEPENDENT KINASE-ACTIVATING KINASE EXISTS IN 3 DISTINCT COMPLEXES

Transcription factor IIH (TFIIH) is a multisubunit complex required fo r transcription and for DNA nucleotide excision repair. TFIIH possesse s three enzymatic activities: (i) an ATP-dependent DNA helicase, (ii) a DNA-dependent ATPase, and (iii) a kinase with specificity for the ca rboxyl-terminal domain of RNA polymerase II. The kinase activity was r ecently identified as the Cdk (cyclin-dependent kinase) activating kin ase, CAK, composed of cdk7, cyclin II, and MAT-1. Here we report the i solation and characterization of three distinct CAK-containing complex es from HeLa nuclear extracts: CAK, a novel CAK-ERCC2 complex, and TFI IH. CAK-ERCC2 can efficiently associate with core-TFIIH to reconstitut e holo-TFIIH transcription activity. We present evidence proposing a c ritical role for ERCC2 in mediating the association of CAK with core T FIIH subunits.