BRCA1 contributes to transcription-coupled repair of DNA damage through polyubiquitination and degradation of Cockayne syndrome B protein.
Open accessAbstract
BRCA1 is an important gene involved in susceptibility to breast and ovarian cancer and its product regulates the cellular response to DNA double-strand breaks. Here, we present evidence that BRCA1 also contributes to the transcription-coupled repair (TCR) of ultraviolet (UV) light-induced DNA damage. BRCA1 immediately accumulates at the sites of UV irradiation-mediated damage in cell nuclei in a manner that is fully dependent on both Cockayne syndrome B (CSB) protein and active transcription. Suppression of BRCA1 expression inhibits the TCR of UV lesions and increases the UV sensitivity of cells proficient in TCR. BRCA1 physically interacts with CSB protein. BRCA1 polyubiquitinates CSB and this polyubiquitination and subsequent degradation of CSB occur following UV irradiation, even in the absence of Cockayne syndrome A (CSA) protein. The depletion of BRCA1 expression increases the UV sensitivity of CSA-deficient cells. These results indicate that BRCA1 is involved in TCR and that a BRCA1-dependent polyubiquitination pathway for CSB exists alongside the CSA-dependent pathway to yield more efficient excision repair of lesions on the transcribed DNA strand.
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ERCC6 degradation following UV irradiation is more rapid in the absence of USP7 or UVSSA.
“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 Wei et al., 2011
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“Further, Mdm4 directly interacts with p53 to disrupts its DNA-binding and transcriptional activation (Francoz et al., 2006; Wei et al., 2016).”
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- Authors
- Wei, L., Lan, L., Yasui, A., Tanaka, K., Saijo, M., Matsuzawa, A., Kashiwagi, R., Maseki, E., Hu, Y., Parvin, J. D., Ishioka, C., & Chiba, N.
- Affiliations
- Tohoku University (JP)
- The University of Osaka (JP)
- The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
- Corresponding author
- Chiba, Natsuko
- Venue
- Cancer Science
- Publisher
- Wiley
- Published
- 2011-08-18
- Volume
- 102
- Issue
- 10
- Pages
- 1840-1847
- ISSN
- 1347-9032 (ISSN-L)
- 1349-7006
- PMC
- PMC11159811
- OpenAlex
- W2066554319
- Cited by
- 48
- References
- 49
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 1 · 2016: 5 · 2015: 7 · 2014: 4 · 2013: 6 · 2012: 5
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Naito Foundation
- Japan Society for the Promotion of Science (22131009, 21591656)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- BRCA1, transcription-coupled repair, UV-induced DNA damage, polyubiquitination, protein degradation, DNA double-strand break repair, UV sensitivity, excision repair
- MeSH terms
- Poly-ADP-Ribose Binding Proteins, DNA, DNA Damage, DNA Repair, DNA Helicases, Humans, Transcription Factors, Ultraviolet Rays, BRCA1 Protein, RNA Interference, RNA, Small Interfering, DNA Repair Enzymes, Cell Line, Tumor, Ubiquitination, Ubiquitinated Proteins, HEK293 Cells
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