CSA-dependent degradation of CSB by the ubiquitin–proteasome pathway establishes a link between complementation factors of the Cockayne syndrome (original) (raw)

  1. Regina Groisman1,3,8,
  2. Isao Kuraoka5,
  3. Odile Chevallier6,
  4. Nogaye Gaye3,
  5. Thierry Magnaldo6,
  6. Kiyoji Tanaka5,
  7. Alexei F. Kisselev2,4,7,
  8. Annick Harel-Bellan3,7, and
  9. Yoshihiro Nakatani1,7
  10. 1 Dana-Farber Cancer Institute,
  11. 2 Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;
  12. 3 UPR9079 CNRS-Ligue Nationale Contre le Cancer, 94800 Villejuif, France;
  13. 4 Norris Cotton Cancer Center and Department of Pharmacology and Toxicology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA;
  14. 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;
  15. 6 Laboratory of Genetic Instability and Cancer, CNRS UPR2169, Institut Gustave Roussy, Villejuif 94805, France
  16. 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.

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