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CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome.
Open accessAbstract
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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“Furthermore, while ERCC6 is degraded in cells following UV irradiation (Groisman et al., 2006; Wei et al., 2011), this degradation is more rapid in the absence of either protein.”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Groisman et al., 2006
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Metadata
- Authors
- Groisman, R., Kuraoka, I., Chevallier, O., Gaye, N., Magnaldo, T., Tanaka, K., Kisselev, A. F., Harel-Bellan, A., & Nakatani, Y.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Japan Science and Technology Agency (JP)
- Dartmouth College (US)
- Dana-Farber Cancer Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2006-06-01
- Volume
- 20
- Issue
- 11
- Pages
- 1429-1434
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1475755
- OpenAlex
- W2143989418
- Cited by
- 268
- References
- 27
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 15 · 2023: 16 · 2022: 10 · 2021: 18 · 2020: 10 · 2019: 14 · 2018: 10 · 2017: 10 · 2016: 14 · 2015: 16 · 2014: 9 · 2013: 12 · 2012: 9
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Leukemia and Lymphoma Society
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- Cockayne syndrome, CSA, CSB, ubiquitin-proteasome system, E3 ubiquitin ligase, transcription-coupled repair, protein degradation, UV-induced DNA damage, DNA repair
- MeSH terms
- Poly-ADP-Ribose Binding Proteins, Cockayne Syndrome, DNA Helicases, Genetic Complementation Test, HeLa Cells, Humans, Transcription Factors, Ubiquitin, DNA Repair Enzymes, Proteasome Endopeptidase Complex
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