Multiomic Analysis of the UV-Induced DNA Damage Response.
Multiomic Analysis of the UV-Induced DNA Damage Response.
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DOI：
10.1016/j.celrep.2016.04.047
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发表时间：
2016-05-17
期刊：
影响因子：
8.8
通讯作者：
Svejstrup JQ
中科院分区：
文献类型：
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作者：
Boeing S;Williamson L;Encheva V;Gori I;Saunders RE;Instrell R;Aygün O;Rodriguez-Martinez M;Weems JC;Kelly GP;Conaway JW;Conaway RC;Stewart A;Howell M;Snijders AP;Svejstrup JQ
为了便于识别细胞对紫外线诱导的DNA损伤的反应中的因素和途径，我们同时进行了几个描述性蛋白质组筛选和一个功能基因组学筛选。当筛选结果叠加在一起并结合生物学知识进行解释时，可以高度自信地识别出许多因素。建立了一个可搜索的数据库BIOBIONAL，它提供了对感兴趣的蛋白质或过程的相关信息的访问，以存储结果并促进数据挖掘。除了揭示许多蛋白质和复合体(包括整合子、粘附素、PHF3、ASC-1、SCAF4、SCAF8和SCAF11)在DNA损伤反应中的作用外，我们还发现了研究较少的黑色素瘤相关丝氨酸/苏氨酸激酶19(STK19)的作用。除了有效地揭示相关因素外，多组体方法还提供了与转录相关的DNA损伤反应相关的各种细胞过程的系统概述。一种多组筛选方法检查了紫外线诱导的DNA损伤反应，多个因素与转录相关的DNA损伤反应有关，黑色素瘤基因STK19是正常DNA损伤反应所必需的，波音等人。通过结合一系列蛋白质组和基因组筛选来研究紫外线诱导的DNA损伤反应。黑色素瘤驱动器STK19的这种反应中的功能以及许多其他因素被揭示。
In order to facilitate the identification of factors and pathways in the cellular response to UV-induced DNA damage, several descriptive proteomic screens and a functional genomics screen were performed in parallel. Numerous factors could be identified with high confidence when the screen results were superimposed and interpreted together, incorporating biological knowledge. A searchable database, bioLOGIC, which provides access to relevant information about a protein or process of interest, was established to host the results and facilitate data mining. Besides uncovering roles in the DNA damage response for numerous proteins and complexes, including Integrator, Cohesin, PHF3, ASC-1, SCAF4, SCAF8, and SCAF11, we uncovered a role for the poorly studied, melanoma-associated serine/threonine kinase 19 (STK19). Besides effectively uncovering relevant factors, the multiomic approach also provides a systems-wide overview of the diverse cellular processes connected to the transcription-related DNA damage response. A multiomic screening approach examines the UV-induced DNA damage response Multiple factors are connected to the transcription-related DNA damage response Melanoma gene STK19 is required for a normal DNA damage response Boeing et al. investigate the UV-induced DNA damage response by combining a range of proteomic and genomic screens. A function in this response for the melanoma driver STK19 as well as a number of other factors are uncovered.