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J Biol Chem. 2017 Apr 21;292(16):6431-6437. doi: 10.1074/jbc.C117.777946. Epub 2017 Mar 14.

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

Author information

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, jlc@stowers.org.
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, rcc@stowers.org.

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

PMID:
28292928
PMCID:
PMC5399097
DOI:
10.1074/jbc.C117.777946
[Indexed for MEDLINE]
Free PMC Article

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