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Identification of a BRCA1-mRNA Splicing Complex Required for Efficient DNA Repair and Maintenance of Genomic Stability
Open accessAbstract
Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.
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RNA splicing factors as oncoproteins and tumour suppressors
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BRCA1–BARD1 promotes RAD51-mediated homologous DNA pairing
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Metadata
- Authors
- Savage, K. I., Gorski, J. J., Barros, E. M., Irwin, G. W., Manti, L., Powell, A. J., Pellagatti, A., Lukashchuk, N., McCance, D. J., McCluggage, W. G., Schettino, G., Salto-Tellez, M., Boultwood, J., Richard, D. J., McDade, S. S., & Harkin, D. P.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 54
- Issue
- 3
- Pages
- 445-459
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1522957007
- Cited by
- 180
- References
- 2
- FWCI
- 7.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- creativecommons.org/licenses/by-nc-nd/3.0/ (vor)
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- The paper
- Savage, K. I., Gorski, J. J., Barros, E. M., Irwin, G. W., Manti, L., Powell, A. J., Pellagatti, A., Lukashchuk, N., McCance, D. J., McCluggage, W. G., Schettino, G., Salto-Tellez, M., Boultwood, J., Richard, D. J., McDade, S. S., & Harkin, D. P. (2014). Identification of a BRCA1-mRNA Splicing Complex Required for Efficient DNA Repair and Maintenance of Genomic Stability. Molecular Cell. https://doi.org/10.1016/j.molcel.2014.03.021
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