Identification of a BRCA1-mRNA Splicing Complex Required for Efficient DNA Repair and Maintenance of Genomic Stability
Data(s) |
08/05/2014
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Resumo |
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. |
Formato |
application/pdf |
Identificador | |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/openAccess |
Fonte |
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 , vol 54 , no. 3 , pp. 445-459 . DOI: 10.1016/j.molcel.2014.03.021 |
Palavras-Chave | #BRCA1, DNA damage, genome stability, DNA repair, mRNA splicing |
Tipo |
article |