Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
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DOI：
10.1016/j.molcel.2012.01.026
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发表时间：
2012-04-27
期刊：
影响因子：
16
通讯作者：
Choudhary, Chunaram
中科院分区：
文献类型：
--
作者：
Beli, Petra;Lukashchuk, Natalia;Wagner, Sebastian A.;Weinert, Brian T.;Olsen, Jesper V.;Baskcomb, Linda;Mann, Matthias;Jackson, Stephen P.;Choudhary, Chunaram
DNA损伤反应（DDR）的调控网络包括许多蛋白质和翻译后修饰。在这里，我们使用基于质谱的蛋白质组学分析系统范围内的响应DNA损伤的平行量化的DDR调节磷酸化蛋白质组，乙酰基组和蛋白质组。我们发现，磷酸化依赖的信号网络的调节更强烈的乙酰化相比。在鉴定的磷酸化蛋白质中，有许多是DNA-PK、ATM和ATR激酶的推定底物，但大多数磷酸化蛋白质不共享ATM/ATR/DNA-PK靶点共识，这表明下游激酶在放大DDR信号中的重要作用。我们发现，剪接调节磷酸酶PPM 1G被招募到DNA损伤的位点，而剪接相关蛋白THRAP 3被排除在这些区域之外。此外，THRAP 3缺失导致细胞对DNA损伤剂的超敏反应，从而表明RNA代谢和DNA修复之间的重要联系。我们的研究结果拓宽了DNA损伤信号网络的知识，并确定了DDR的新组件。
The regulatory networks of the DNA damage response (DDR) encompass many proteins and posttranslational modifications. Here, we use mass spectrometry-based proteomics to analyze the systems-wide response to DNA damage by parallel quantification of the DDR-regulated phosphoproteome, acetylome and proteome. We show that phosphorylation-dependent signaling networks are regulated more strongly compared to acetylation. Among the phosphorylated proteins identified are many putative substrates of DNA-PK, ATM and ATR kinases, but a majority of phosphorylated proteins do not share the ATM/ATR/DNA-PK target consensus, suggesting an important role of downstream kinases in amplifying DDR signals. We show that the splicing-regulator phosphatase PPM1G is recruited to sites of DNA damage, while the splicing-associated protein THRAP3 is excluded from these regions. Moreover, THRAP3 depletion causes cellular hypersensitivity to DNA damaging agents, thus suggesting an important link between RNA metabolism and DNA repair. Our results broaden the knowledge of DNA damage signaling networks and identify novel components of the DDR.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
64.5
作者：
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通讯作者：
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DOI：
10.1016/j.tripleo.2010.11.020
发表时间：
2011-05-01
期刊：
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY
影响因子：
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作者：
Cha, Jeong-Dan;Kim, Hyung Jun;Cha, In-Ho
通讯作者：
Cha, In-Ho
影响因子：
21.3
作者：
Jazayeri, A;Falck, J;Jackson, SP
通讯作者：
Jackson, SP
影响因子：
64.8
作者：
Brummelkamp, TR;Nijman, SMB;Bernards, R
通讯作者：
Bernards, R