Damage control: DNA repair, transcription, and the ubiquitin–proteasome system

The presence of DNA damage within an actively transcribed gene poses an immediate threat to cellular viability. Bulky DNA adducts, such as those induced by ultraviolet light, can profoundly influence patterns of gene expression by causing the irreversible arrest of RNA polymerase II at sites of DNA damage. It is critical that processes exist to either specifically repair transcribed genes or clear stalled RNA polymerase, so that general repair can occur and transcription resume. A growing body of evidence indicates that clearance of stalled polymerase is achieved, in part, by ubiquitin-mediated destruction of the largest subunit of RNA polymerase II. In this review, we shall discuss how an intimate connection between RNA polymerase II and the ubiquitylation machinery acts to restore normal transcription after DNA damage, and other forms of transcriptional arrest, has occurred.