Molecular Cell
Volume 54, Issue 3, 8 May 2014, Pages 445-459
Journal home page for Molecular Cell

Article
Identification of a BRCA1-mRNA Splicing Complex Required for Efficient DNA Repair and Maintenance of Genomic Stability

https://doi.org/10.1016/j.molcel.2014.03.021Get rights and content
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Highlights

  • BRCA1 forms a complex with mRNA splicing proteins following DNA damage

  • The BRCA1-mRNA splicing complex promotes the stability of genes involved in the DDR

  • BRCA1-dependent splicing of DDR genes maintains their protein expression

  • The BRCA1-mRNA splicing complex is required for DNA repair and genomic stability

Summary

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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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).