Site-specific Phosphorylation Dynamics of the Nuclear Proteome during the DNA Damage Response
Site-specific Phosphorylation Dynamics of the Nuclear Proteome during the DNA Damage Response
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DOI：
10.1074/mcp.m900616-mcp200
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发表时间：
2010-06-01
影响因子：
7
通讯作者：
Andersen, Jens S.
中科院分区：
文献类型：
--
作者：
Bennetzen, Martin V.;Larsen, Dorthe Helena;Andersen, Jens S.
为了研究DNA损伤反应的时间调控，我们应用基于定量质谱的蛋白质组学技术来测量电离辐射后核蛋白的位点特异性磷酸化变化。我们在DNA损伤后的5个时间点分析了5204个磷酸化位点，其中209个蛋白上的594个位点被调节超过2倍。在594个位点中，372个是主要来源于核的新型磷酸化位点。这594个站点可以被划分为不同的时间剖面。辐射后不久调节的位点在共济失调毛细血管扩张突变（ATM）激酶SQ一致序列基序和一个新的SXXQ基序中富集。重要的是，除了诱导磷酸化外，我们还发现了一组相当多的位点经历DNA损伤诱导的去磷酸化。总之，我们的数据扩展了DNA损伤调控的已知磷酸化位点的数量，提供了迄今为止前所未有的DNA损伤修饰磷酸化事件的时间解剖，并阐明了在多方面DNA损伤反应的动态调节中不同类型的翻译后修饰之间的串音。中国生物医学工程学报（英文版），2010。
To investigate the temporal regulation of the DNA damage response, we applied quantitative mass spectrometry-based proteomics to measure site-specific phosphorylation changes of nuclear proteins after ionizing radiation. We profiled 5204 phosphorylation sites at five time points following DNA damage of which 594 sites on 209 proteins were observed to be regulated more than 2-fold. Of the 594 sites, 372 are novel phosphorylation sites primarily of nuclear origin. The 594 sites could be classified to distinct temporal profiles. Sites regulated shortly after radiation were enriched in the ataxia telangiectasia mutated (ATM) kinase SQ consensus sequence motif and a novel SXXQ motif. Importantly, in addition to induced phosphorylation, we identified a considerable group of sites that undergo DNA damage-induced dephosphorylation. Together, our data extend the number of known phosphorylation sites regulated by DNA damage, provides so far unprecedented temporal dissection of DNA damage-modified phosphorylation events, and elucidate the cross-talk between different types of post-translational modifications in the dynamic regulation of a multifaceted DNA damage response. Molecular & Cellular Proteomics 9:1314-1323, 2010.