Image removed for copyright considerations. Figure 2 in Muratani M, Tansey WP. "How the ubiquitin-proteasome system controls transcription." Nat Rev Mol Cell Biol. 2003 Mar;4(3):192-201. Regulation of TCR by ubiquitylation of RNA polymerase II. Transcription-coupled repair (TCR) is the mechanism through which mutations in actively transcribed genes are preferentially repaired. a | Elongating RNA polymerase II (pol II), which has a unique pattern of phosphorylation on its carboxy-terminal domain (CTD), encounters a damaged DNA segment. The stalled polymerase (b) then recruits the ubiquitin (Ub)-ligase Rsp5 (c), which in turn ubiquitylates the largest subunit of pol II in a CTD-phosphorylation-dependent manner. d | Ubiquitylation is followed by the proteasomal destruction of at least one subunit of polymerase, recruitment of the repair machinery and restoration of DNA integrity. Image removed for copyright considerations. Source: Figure 5 in Muratani M, Tansey WP. "How the ubiquitin-proteasome system controls transcription." Nat Rev Mol Cell Biol. 2003 Mar;4(3):192-201. The ubiquitin (Ub)–proteasome system regulates transcription at numerous levels. a | Interactions of an activator with the general transcriptional machinery (green) functions to b | recruit ubiquitin ligase(s) to the site of transcription and ubiquitylates many factors, including the activator, RNA polymerase II (pol II) and histones. c | These ubiquitylation events in turn recruit the 26S proteasome, which d | simultaneously destroys the activator and promotes elongation of transcription by pol II. Importantly, this proposed mechanism limits uncontrolled transcription in two ways — by destroying the activator at each cycle of promoter 'firing' and by ensuring that interactions between pol II and the proteasome are made in an activator- and promoter-dependent manner.