CSB-Dependent Cyclin-Dependent Kinase 9 Degradation and RNA Polymerase II Phosphorylation during Transcription-Coupled Repair.

ABSTRACT

DNA lesions block cellular processes such as transcription, inducing apoptosis, tissue failures, and premature aging. To counteract the deleterious effects of DNA damage, cells are equipped with various DNA repair pathways. Transcription-coupled repair specifically removes helix-distorting DNA adducts in a coordinated multistep process. This process has been extensively studied; however, once the repair reaction is accomplished, little is known about how transcription restarts. In this study, we show that, after UV irradiation, the cyclin-dependent kinase 9 (CDK9)/cyclin T1 kinase unit is specifically released from the HEXIM1 complex and that this released fraction is degraded in the absence of the Cockayne syndrome group B protein (CSB). We determine that UV irradiation induces a specific Ser2 phosphorylation of the RNA polymerase II and that this phosphorylation is CSB dependent. Surprisingly, CDK9 is not responsible for this phosphorylation but instead might play a nonenzymatic role in transcription restart after DNA repair.