Abstract
The transcription/DNA repair factor TFIIH may be resolved into at least two subcomplexes: the core TFIIH and the cdk-activating kinase (CAK) complex. The CAK complex, which is also found free in the cell, is composed of cdk7, cyclin H, and MAT1. In the present work, we found that the C terminus of MAT1 binds to the cdk7 x cyclin H complex and activates the cdk7 kinase activity. The median portion of MAT1, which contains a coiled-coil motif, allows the binding of CAK to the TFIIH core through interactions with both XPD and XPB helicases. Furthermore, using recombinant TFIIH complexes, it is demonstrated that the N-terminal RING finger domain of MAT1 is crucial for transcription activation and participates to the phosphorylation of the C-terminal domain of the largest subunit of the RNA polymerase II.
Highlights
Cyclin-dependent kinases1 have a central role in the coordination of the eukaryotic cell cycle and participate in the integration of diverse growth regulatory signals
We demonstrate here that MAT1 interacts with the cdk-activating kinase (CAK) complex through the hydrophobic C-terminal domain and that this region is sufficient to activate cdk7 kinase activity towards synthetic ctd4 or cdk2 substrates
The cdk7 Activation Domain of MAT1 Resides in Its C Terminus—MAT1 was able to interact separately with either cdk7 or cyclin H and much more strongly when it was coexpressed with cdk7 and cyclin H
Summary
Cyclin-dependent kinases (cdk) have a central role in the coordination of the eukaryotic cell cycle and participate in the integration of diverse growth regulatory signals. Some members of this protein kinase family are involved in cell cycle control and in other mechanisms that govern cell life, notably transcription. As part of the multienzymatic protein complex TFIIH, CAK, in coordination with the XPB and XPD helicases, participates in various events of the transcription reaction. When the CAK complex is free, cdk preferentially phosphorylates cdk, another member of the cyclin-dependent kinase family, whereas when part of TFIIH, a preferential and specific phosphorylation of the CTD of RNA pol II is observed [13, 15].
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