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 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.

• Authors: 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
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 292 Issue 16 Pg. 6431-6437 (04 21 2017) ISSN: 1083-351X [Electronic] United States
• PMID: 28292928 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Alpha-Amanitin
• CUL5 protein, human
• Cullin Proteins
• ELOA protein, human
• Elongin
• Poly-ADP-Ribose Binding Proteins
• Transcription Factors
• Green Fluorescent Proteins
• Ubiquitin-Protein Ligases
• RNA Polymerase II
• DNA Helicases
• ERCC6 protein, human
• DNA Repair Enzymes

Topics

• Alpha-Amanitin (metabolism)
• Cell Line
• Cullin Proteins (metabolism)
• DNA Damage
• DNA Helicases (metabolism)
• DNA Repair
• DNA Repair Enzymes (metabolism)
• Elongin
• Fluorescence Resonance Energy Transfer
• Green Fluorescent Proteins (metabolism)
• Humans
• Image Processing, Computer-Assisted
• Mutation
• Plasmids (metabolism)
• Poly-ADP-Ribose Binding Proteins
• RNA Polymerase II (metabolism)
• Transcription Factors (genetics, metabolism)
• Ubiquitin-Protein Ligases (metabolism)