University Hospital Cologne, Center for Internal Medicine, Division of Hematology and Oncology, Cologne, Germany.
Cell Cycle. 2011 Jan 1;10(1):23-7. doi: 10.4161/cc.10.1.14351.
In response to DNA damage, cells activate a complex, kinase-based signaling network that consist of two components--a rapid phosphorylation-driven signaling cascade that results in immediate inhibition of Cdk/cyclin complexes to arrest the cell cycle along with recruitment of repair machinery to damaged DNA, followed by a delayed transcriptional response that promotes cell cycle arrest through the induction of Cdk inhibitors, such as p21. In recent years a third layer of complexity has emerged that involves post-transcriptional control of mRNA stability, splicing, and translation as a critical part of the DNA damage response. Here, we describe recent work implicating DNA damage-dependent modification of RNA-binding proteins that are responsible for some of these mRNA effects, highlighting recent work on post-transcriptional regulation of the cell cycle checkpoint protein/apoptosis inducer Gadd45a by the checkpoint kinase MAPKAP Kinase-2.
针对 DNA 损伤，细胞激活了一个由激酶组成的复杂信号网络，该网络由两个组件组成——一个快速的磷酸化驱动的信号级联反应，导致 Cdk/周期蛋白复合物的立即抑制，从而阻止细胞周期，并招募修复机制到受损的 DNA，随后是延迟的转录反应，通过诱导 Cdk 抑制剂（如 p21）促进细胞周期停滞。近年来，出现了第三个复杂性层面，涉及 mRNA 稳定性、剪接和翻译的转录后控制，这是 DNA 损伤反应的关键部分。在这里，我们描述了最近的工作，这些工作表明 RNA 结合蛋白的 DNA 损伤依赖性修饰是这些 mRNA 效应的一部分，并强调了检查点激酶 MAPKAP Kinase-2 对细胞周期检查点蛋白/凋亡诱导因子 Gadd45a 的转录后调节的最新工作。
