2. Academic Validation
  3. Cockayne syndrome B protein regulates recruitment of the Elongin A ubiquitin ligase to sites of DNA damage

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

  • J Biol Chem. 2017 Apr 21;292(16):6431-6437. doi: 10.1074/jbc.C117.777946.
Juston C Weems 1,  Brian D Slaughter 1,  Jay R Unruh 1,  Stefan Boeing 2,  Shawn M Hall 1,  Merry B McLaird 1,  Takashi Yasukawa 3,  Teijiro Aso 3,  Jesper Q Svejstrup 2,  Joan W Conaway 4 5,  Ronald C Conaway 6 5
Affiliations

Affiliations

  • 1 From the Stowers Institute for Medical Research, Kansas City, Missouri 64110.
  • 2 the Mechanisms of Transcription Laboratory, The Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, United Kingdom.
  • 3 the Department of Functional Genomics, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan.
  • 4 From the Stowers Institute for Medical Research, Kansas City, Missouri 64110, [email protected].
  • 5 the Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, and.
  • 6 From the Stowers Institute for Medical Research, Kansas City, Missouri 64110, [email protected].
PMID: 28292928 DOI: 10.1074/jbc.C117.777946
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 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.

Keywords

DNA repair; E3 ubiquitin ligase; RNA polymerase II; nucleotide excision repair; transcription.

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