J. Biol. Chem.-2017-Weems-6431-7.pdf (875.51 kB)

Cockayne syndrome B protein regulates recruitment of the Elongin A ubiquitin ligase to sites of DNA damage

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posted on 15.10.2020 by Juston C Weems, Brian D Slaughter, Jay R Unruh, Stefan Boeing, Shawn M Hall, Merry B McLaird, Takashi Yasukawa, Teijiro Aso, Jesper Q Svejstrup, Joan W Conaway, Ronald C Conaway
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. In addition, we present evidence that the CSB protein promotes stable recruitment of the Elongin A ubiquitin ligase to sites of DNA damage. Our findings are consistent with the model that the Elongin A ubiquitin ligase and the CSB protein function together in a common pathway in response to Pol II stalling and DNA damage.

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