CSA-dependent degradation of CSB by the ubiquitin–proteasome pathway establishes a link between complementation factors of the Cockayne syndrome
- Regina Groisman1,3,8,
- Isao Kuraoka5,
- Odile Chevallier6,
- Nogaye Gaye3,
- Thierry Magnaldo6,
- Kiyoji Tanaka5,
- Alexei F. Kisselev2,4,7,
- Annick Harel-Bellan3,7, and
- Yoshihiro Nakatani1,7
- 1 Dana-Farber Cancer Institute,
- 2 Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 3 UPR9079 CNRS-Ligue Nationale Contre le Cancer, 94800 Villejuif, France;
- 4 Norris Cotton Cancer Center and Department of Pharmacology and Toxicology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA;
- 5 Graduate School of Frontier Biosciences, Osaka University, and Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Suita, Osaka 565-0871, Japan;
- 6 Laboratory of Genetic Instability and Cancer, CNRS UPR2169, Institut Gustave Roussy, Villejuif 94805, France
- 7
↵7 These authors contributed equally to this work.
Abstract
Mutations in the CSA or CSB complementation genes cause the Cockayne syndrome, a severe genetic disorder that results in patients’ death in early adulthood. CSA and CSB act in a transcription-coupled repair (TCR) pathway, but their functional relationship is not understood. We have previously shown that CSA is a subunit of an E3 ubiquitin ligase complex. Here we demonstrate that CSB is a substrate of this ligase: Following UV irradiation, CSB is degraded at a late stage of the repair process in a proteasome- and CSA-dependent manner. Moreover, we demonstrate the importance of CSB degradation for post-TCR recovery of transcription and for the Cockayne syndrome. Our results unravel for the first time the functional relationship between CSA and CSB.
Keywords
Footnotes
- 8
↵8 Corresponding author.
↵8 E-MAIL groisman{at}vjf.cnrs.fr; FAX 33-1-49583307.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.378206
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- Received December 30, 2005.
- Accepted March 27, 2006.
- Copyright © 2006, Cold Spring Harbor Laboratory Press
