Cockayne syndrome B protein regulates recruitment of the elongin a ubiquitin ligase to sites of DNA damage

Abstract

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 ElonginAubiquitin ligase and its recruitment to sites ofDNAdamage 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 byDNA-damagingagentsand α-Amanitin. In addition,we present evidence that theCSBproteinpromotesstable recruitment of the ElonginAubiquitin ligase to sites ofDNAdamage. Our findings are consistent with the model that the Elongin A ubiquitin ligase and theCSBprotein function together in acommonpathway in response to Pol II stalling and DNA damage.