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首页> 外文期刊>Nature cell biology >A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response
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A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response

机译：全基因组同源重组筛选确定RNA结合蛋白RBMX为DNA损伤反应的组成部分

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摘要

Repair of DNA double-strand breaks is critical to genomic stability and the prevention of developmental disorders and cancer. A central pathway for this repair is homologous recombination (HR). Most knowledge of HR is derived from work in prokaryotic and eukaryotic model organisms. We carried out a genome-wide siRNA-based screen in human cells. Among positive regulators of HR we identified networks of DNA-damage-response and pre-mRNA-processing proteins, and among negative regulators we identified a phosphatase network. Three candidate proteins localized to DNA lesions, including RBMX, a heterogeneous nuclear ribonucleoprotein that has a role in alternative splicing. RBMX accumulated at DNA lesions through multiple domains in a poly(ADP-ribose) polymerase 1-dependent manner and promoted HR by facilitating proper BRCA2 expression. Our screen also revealed that off-target depletion of RAD51 is a common source of RNAi false positives, raising a cautionary note for siRNA screens and RNAi-based studies of HR.
机译：DNA双链断裂的修复对于基因组稳定性以及预防发育障碍和癌症至关重要。这种修复的主要途径是同源重组（HR）。 HR的大多数知识都来自于原核和真核模型生物。我们在人类细胞中进行了全基因组的基于siRNA的筛选。在HR的正调节剂中，我们确定了DNA损伤反应和mRNA加工前蛋白的网络，而在负调节剂中，我们确定了磷酸酶的网络。定位于DNA损伤的三种候选蛋白，包括RBMX，一种异质核糖核蛋白，在可变剪接中起作用。 RBMX以多聚（ADP-核糖）聚合酶1依赖性方式通过多个域在DNA损伤处积累，并通过促进适当的BRCA2表达而促进HR。我们的筛查还显示，RAD51的脱靶消耗是RNAi假阳性的常见来源，这为siRNA筛查和基于RNAi的HR研究提出了警告。

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