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.
Groisman
Regina
R
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. groisman@vjf.cnrs.fr
Kuraoka
Isao
I
Chevallier
Odile
O
Gaye
Nogaye
N
Magnaldo
Thierry
T
Tanaka
Kiyoji
K
Kisselev
Alexei F
AF
Harel-Bellan
Annick
A
Nakatani
Yoshihiro
Y
D003057:Cockayne Syndrome / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
C095472:ERCC8 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D014157:Transcription Factors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes