Abstract：
: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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Savage KI,Gorski JJ,Barros EM,Irwin GW,Manti L,Powell AJ,Pellagatti A,Lukashchuk N,McCance DJ,McCluggage WG,Schettino G,Salto-Tellez M,Boultwood J,Richard DJ,McDade SS,Harkin DPdoi
10.1016/j.molcel.2014.03.021subject
Has Abstractpub_date
2014-05-08 00:00:00pages
445-59issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(14)00253-6journal_volume
54pub_type
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