Gene Regulation
A role for the Cockayne Syndrome B (CSB)-Elongin ubiquitin ligase complex in signal-dependent RNA polymerase II transcription
The Elongin complex was originally identified as an RNA polymerase II (RNAPII) elongation factor and subsequently as the substrate recognition component of a Cullin-RING E3 ubiquitin ligase. More recent evidence indicates that the Elongin ubiquitin ligase assembles with the Cockayne syndrome B helicase (CSB) in response to DNA damage and can target stalled polymerases for ubiquitylation and removal from the genome. In this report, we present evidence that the CSB-Elongin ubiquitin ligase pathway has roles beyond the DNA damage response in the activation of RNAPII-mediated transcription.Cockayne syndrome B protein regulates recruitment of the Elongin A ubiquitin ligase to sites of DNA damage
Elongin A performs dual functions as the transcriptionally active subunit of RNA polymerase II (Pol II) elongation factor Elongin and as the substrate recognition subunit of a Cullin-RING E3 ubiquitin ligase that ubiquitylates Pol II in response to DNA damage. Assembly of the Elongin A ubiquitin ligase and its recruitment to sites of DNA damage is a tightly regulated process induced by DNA-damaging agents and α-amanitin, a drug that induces Pol II stalling. In this study, we demonstrate (i) that Elongin A and the ubiquitin ligase subunit CUL5 associate in cells with the Cockayne syndrome B (CSB) protein and (ii) that this interaction is also induced by DNA-damaging agents and α-amanitin.Assembly of the Elongin A Ubiquitin Ligase Is Regulated by Genotoxic and Other Stresses
Background: Elongin is both a Pol II elongation factor and part of a ubiquitin ligase targeting stalled Pol II.Results: Elongin ubiquitin ligase assembly is driven by signals that provoke Pol II stalling and/or activate Elongin-dependent transcription.Conclusion: Elongin ligase assembly is a regulated process.Significance: This study provides insight into Elongin ubiquitin ligase functions and general mechanisms of ubiquitin ligase activation.
