ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
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DOI：
10.1126/science.1140321
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发表时间：
2007-05-25
期刊：
影响因子：
56.9
通讯作者：
Elledge, Stephen J.
中科院分区：
文献类型：
--
作者：
Matsuoka, Shuhei;Ballif, Bryan A.;Elledge, Stephen J.
细胞对DNA损伤的反应由许多蛋白激酶介导，包括ATM（共济失调毛细血管扩张突变）和ATR（ATM和Rad3相关）。该途径的信号转导部分的轮廓是已知的，但对DNA损伤反应（DDR）的生理范围知之甚少。我们进行了大规模的蛋白质组学分析的蛋白质磷酸化响应的DNA损伤的共识网站识别的ATM和ATR，并确定了超过900个调节磷酸化位点，涵盖700多个蛋白质。该数据集的子集的功能分析表明，该列表高度富集了DDR中涉及的蛋白质。这组蛋白质是高度互连的，我们发现了大量以前没有与DDR连接的蛋白质模块和网络。该数据库为DDR描绘了比以前更广阔的前景，并开辟了调查哺乳动物DNA损伤反应的新途径。
Cellular responses to DNA damage are mediated by a number of protein kinases, including ATM ( ataxia telangiectasia mutated) and ATR ( ATM and Rad3-related). The outlines of the signal transduction portion of this pathway are known, but little is known about the physiological scope of the DNA damage response (DDR). We performed a large-scale proteomic analysis of proteins phosphorylated in response to DNA damage on consensus sites recognized by ATM and ATR and identified more than 900 regulated phosphorylation sites encompassing over 700 proteins. Functional analysis of a subset of this data set indicated that this list is highly enriched for proteins involved in the DDR. This set of proteins is highly interconnected, and we identified a large number of protein modules and networks not previously linked to the DDR. This database paints a much broader landscape for the DDR than was previously appreciated and opens new avenues of investigation into the responses to DNA damage in mammals.