对DNA-PKcs信号的深度测绘揭示了其基因特征的保存特征
Shannon Marshall1, Marcos V A S Navarro1,2, Carolline F R Ascenҫão1
11. Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
bioRxiv : the preprint server for biology
|January 31, 2024
概括
DNA-PKcs是一种DNA损伤传感器,调节基因表达和复制. 研究人员发现了一种新的酸化基因,揭示了DNA-PKcs在DNA修复和细胞过程中的新基质和功能.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- DNA-PKcs是DNA双链断裂修复中的关键激酶.
- 新出现的证据表明,DNA-PKcs也调节了转录,翻译和DNA复制.
- 这些更广泛的功能中介的特定基质在很大程度上是未知的.
研究的目的:
- 为了全面地绘制DNA-PKcs信号通路,以响应电离辐射.
- 为了确定DNA-PKcs.的新基质和调节机制.
- 为了研究DNA-PKcs和ATM激酶信号传递之间的相互作用.
主要方法:
- 量化蛋白组学被用于描述信号事件.
- 电离辐射被用来诱导DNA损伤.
- 在小鼠和人类细胞系中进行了跨物种分析.
主要成果:
- 产生了DNA-PKcs信号传输的高覆盖地图.
- 发现了DNA-PKcs的新型非正规化动机 (S/T-ψ-D/E),与正规的S/T-Q动机不同.
- 发现,在这种新型动机中,剪接因子和转录调节剂,包括具有SAP域的,被酸化.
结论:
- 这项研究扩大了DNA-PKcs和ATM已知的基质谱.
- 对于DNA-PKcs,一种新的优先酸化基因为其在DNA修复之外的作用提供了机械的洞察力.
- 这些发现将DNA-PKcs与通过新型基质的核酸代谢和蛋白质相互作用联系起来.
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