RNA/DNA Hybrid Interactome Identifies DXH9 as a Molecular Player in Transcriptional Termination and R-Loop-Associated DNA Damage.
RNA/DNA Hybrid Interactome Identifies DXH9 as a Molecular Player in Transcriptional Termination and R-Loop-Associated DNA Damage.
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DOI：
10.1016/j.celrep.2018.04.025
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发表时间：
2018-05-08
期刊：
影响因子：
8.8
通讯作者：
Gromak N
中科院分区：
文献类型：
--
作者：
Cristini A;Groh M;Kristiansen MS;Gromak N
R环包含RNA/DNA杂合体和置换的单链DNA。它们发挥着重要的生物学作用，并与病理学有关。即便如此，识别这些结构的蛋白质在很大程度上是不确定的。使用亲和纯化与S9.6抗体偶联质谱，我们确定了RNA/DNA杂交相互作用组在HeLa细胞。这包括已知的R环相关因子SRSF 1、FACT和Top1，以及尚未表征的相互作用因子，包括解旋酶、RNA加工、DNA修复和染色质因子。我们验证这些相互作用的具体例子，并表征其参与R-环生物学。最佳候选DHX 9解旋酶促进R环抑制和转录终止。DHX 9与PARP 1相互作用，这两种蛋白质都能防止R环相关的DNA损伤。DHX 9和其他相互作用体解旋酶在癌症中过表达，将R环介导的DNA损伤和疾病联系起来。我们的RNA/DNA杂交相互作用组为研究健康和疾病中的R环生物学提供了强大的资源。质谱鉴定人类细胞中的RNA/DNA杂合相互作用组顶部RNA/DNA相互作用组候选物DHX 9促进R环抑制DHX 9调节转录终止DHX 9与PARP 1相互作用并防止R环相关的DNA损伤Cristini et al.使用亲和纯化和质谱法来定义人类细胞中的RNA/DNA相互作用组，并通过揭示DHX 9在转录终止和R环相关DNA损伤中的作用来验证它。
R-loops comprise an RNA/DNA hybrid and displaced single-stranded DNA. They play important biological roles and are implicated in pathology. Even so, proteins recognizing these structures are largely undefined. Using affinity purification with the S9.6 antibody coupled to mass spectrometry, we defined the RNA/DNA hybrid interactome in HeLa cells. This consists of known R-loop-associated factors SRSF1, FACT, and Top1, and yet uncharacterized interactors, including helicases, RNA processing, DNA repair, and chromatin factors. We validate specific examples of these interactors and characterize their involvement in R-loop biology. A top candidate DHX9 helicase promotes R-loop suppression and transcriptional termination. DHX9 interacts with PARP1, and both proteins prevent R-loop-associated DNA damage. DHX9 and other interactome helicases are overexpressed in cancer, linking R-loop-mediated DNA damage and disease. Our RNA/DNA hybrid interactome provides a powerful resource to study R-loop biology in health and disease. Mass spectrometry identifies the RNA/DNA hybrid interactome in human cells Top RNA/DNA interactome candidate DHX9 promotes R-loop suppression DHX9 regulates transcriptional termination DHX9 interacts with PARP1 and prevents R-loop-associated DNA damage Cristini et al. use affinity purification and mass spectrometry to define the RNA/DNA interactome in human cells and validate it by revealing the role of DHX9 in transcriptional termination and R-loop-associated DNA damage.
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影响因子：
14.9
作者：
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