Quantitative Proteomic Atlas of Ubiquitination and Acetylation in the DNA Damage Response.
Quantitative Proteomic Atlas of Ubiquitination and Acetylation in the DNA Damage Response.
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DOI：
10.1016/j.molcel.2015.05.006
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发表时间：
2015-09-03
期刊：
影响因子：
16
通讯作者：
Elledge SJ
中科院分区：
文献类型：
--
作者：
Elia AE;Boardman AP;Wang DC;Huttlin EL;Everley RA;Dephoure N;Zhou C;Koren I;Gygi SP;Elledge SJ
DNA损伤反应（DDR）的执行依赖于蛋白质修饰的动态阵列。利用定量蛋白质组学，我们已经在全球范围内分析了紫外线和电离辐射对泛素化、乙酰化和磷酸化的影响。为了改善乙酰化位点分析，我们开发了FACET-IP策略。我们的33，500个泛素化和16，740个乙酰化位点的数据集为蛋白质组的DDR重塑提供了有价值的见解。我们发现，K6-和K33-连接的多聚泛素化在DNA损伤后大量增加，这增加了这些连接主要致力于DDR功能的可能性。我们还表明，Cullin环连接酶介导10%的DNA损伤诱导的泛素化事件，EXO 1是SCF-细胞周期蛋白F底物在响应紫外线辐射。我们广泛的数据集揭示了已知DDR参与者（如PCNA）上的其他受调控位点，并确定了以前未知的DDR靶点（如CENP），强调了DDR对细胞生理学的广泛影响。
Execution of the DNA damage response (DDR) relies upon a dynamic array of protein modifications. Using quantitative proteomics, we have globally profiled ubiquitination, acetylation, and phosphorylation in response to ultraviolet and ionizing radiation. To improve acetylation site profiling, we developed the strategy FACET-IP. Our datasets of 33,500 ubiquitination and 16,740 acetylation sites provide valuable insight into DDR remodeling of the proteome. We find that K6- and K33-linked polyubiquitination undergo bulk increases in response to DNA damage, raising the possibility that these linkages are largely dedicated to DDR function. We also show that Cullin Ring Ligases mediate 10% of DNA damage induced ubiquitination events and that EXO1 is an SCF-Cyclin F substrate in the response to UV radiation. Our extensive datasets uncover additional regulated sites on known DDR players such as PCNA and identify previously unknown DDR targets such as CENPs, underscoring the broad impact of the DDR on cellular physiology.