CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome.

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.

• Authors: Regina Groisman, Isao Kuraoka, Odile Chevallier, Nogaye Gaye, Thierry Magnaldo, Kiyoji Tanaka, Alexei F Kisselev, Annick Harel-Bellan, Yoshihiro Nakatani
• Journal: Genes & development (Genes Dev) Vol. 20 Issue 11 Pg. 1429-34 (Jun 01 2006) ISSN: 0890-9369 [Print] United States
• PMID: 16751180 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ERCC8 protein, human
• Poly-ADP-Ribose Binding Proteins
• Transcription Factors
• Ubiquitin
• Proteasome Endopeptidase Complex
• DNA Helicases
• ERCC6 protein, human
• DNA Repair Enzymes

Topics

• Cockayne Syndrome (genetics)
• DNA Helicases (genetics, metabolism)
• DNA Repair Enzymes (genetics, metabolism)
• Genetic Complementation Test
• HeLa Cells
• Humans
• Poly-ADP-Ribose Binding Proteins
• Proteasome Endopeptidase Complex (metabolism)
• Transcription Factors (genetics, metabolism)
• Ubiquitin (metabolism)