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

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.
Mesh Terms:
Cockayne Syndrome, DNA Helicases, DNA Repair Enzymes, Genetic Complementation Test, HeLa Cells, Humans, Proteasome Endopeptidase Complex, Transcription Factors, Ubiquitin
Genes Dev.
Date: Jun. 01, 2006
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