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首页> 外文期刊>Molecular cell >Identification of a BRCA1-mRNA Splicing Complex Required for Efficient DNA Repair and Maintenance of Genomic Stability
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Identification of a BRCA1-mRNA Splicing Complex Required for Efficient DNA Repair and Maintenance of Genomic Stability

机译：高效DNA修复和基因组稳定性维持所需的BRCA1-mRNA剪接复合体的鉴定。

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摘要

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.
机译：BRCA1内的突变使携带者容易患乳腺癌和卵巢癌。 BRCA1通过组装涉及DNA修复，细胞周期阻滞和转录调控的多种蛋白质复合物来维持基因组稳定性。在这里，我们报告鉴定包含BCLAF1和mRNA剪接机制其他关键成分的DNA损伤诱导的BRCA1蛋白复合物。响应DNA损伤，该复合物调节参与DNA损伤信号传导和修复的许多基因的mRNA剪接，从而促进这些转录物/蛋白质的稳定性。此外，我们表明废除这种复合物会导致对DNA损伤，缺陷DNA修复和基因组不稳定的敏感性。有趣的是，已在多种癌症类型中发现了在这种复合物中发现的许多蛋白质中的突变。这些数据表明，BRCA1-mRNA剪接复合体对剪接的调控在细胞对DNA损伤的反应中起着重要作用。

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