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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.

Original publication




Journal article


Mol Cell

Publication Date





445 - 459


Adaptor Proteins, Signal Transducing, BRCA1 Protein, Basic-Leucine Zipper Transcription Factors, Cell Survival, DNA Damage, DNA Repair, DNA Repair Enzymes, DNA-Binding Proteins, Exodeoxyribonucleases, Fanconi Anemia Complementation Group Proteins, Genome, Human, Genomic Instability, HEK293 Cells, Humans, Phosphorylation, Protein Processing, Post-Translational, RNA Splicing, RNA, Messenger, Radiation Tolerance, Repressor Proteins, Tumor Suppressor Proteins