iTRAQ-based chromatin proteomic screen reveals CHD4-dependent recruitment of MBD2 to sites of DNA damage
iTRAQ-based chromatin proteomic screen reveals CHD4-dependent recruitment of MBD2 to sites of DNA damage
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基于 iTRAQ 的染色质蛋白质组学筛选揭示了 MBD2 依赖于 CHD4 募集到 DNA 损伤位点。
DOI：
10.1016/j.bbrc.2016.01.162
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Guo Caixia
中科院分区：
文献类型：
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作者：
Sun Yazhou;Yang Yeyan;Shen Hongyan;Wang Zhifeng;Liu Yang;Zhang Hui;Tang TieShan;Guo Caixia
许多DNA修复蛋白可以在遗传毒性应激时被募集到DNA损伤位点。为了寻找潜在的DNA修复蛋白参与细胞反应丝裂霉素C治疗，我们利用定量蛋白质组发现的蛋白质，表现出差异富集在染色质部分DNA损伤后。共鉴定出397个蛋白质，GO分析显示其中有许多因子参与染色质修饰和DNA修复。甲基CpG结合域蛋白2（MBD 2）在激光照射后被募集到DNA损伤位点，其募集是通过MBD结构域和MBD 2 C端介导的。此外，MBD 2的募集依赖于聚（ADP-核糖）和染色体结构域解旋酶DNA结合蛋白4（CHD 4）。此外，通过CRISPR-Cas9技术敲低MBD 2导致哺乳动物细胞中的MMC敏感性。
Many DNA repair proteins can be recruited to DNA damage sites upon genotoxic stress. In order to search potential DNA repair proteins involved in cellular response to mitomycin C treatment, we utilized a quantitative proteome to uncover proteins that manifest differentially enrichment in the chromatin fraction after DNA damage. 397 proteins were identified, among which many factors were shown to be involved in chromatin modification and DNA repair by GO analysis. Specifically, methyl-CpG-binding domain protein 2 (MBD2) is revealed to be recruited to DNA damage sites after laser microirradiation, which was mediated through MBD domain and MBD2 C-terminus. Additionally, the recruitment of MBD2 is dependent on poly (ADP-ribose) and chromodomain helicase DNA-binding protein 4 (CHD4). Moreover, knockdown of MBD2 by CRISPR-Cas9 technique results in MMC sensitivity in mammalian cells.