Risk Assessment, Detection, and Intervention Program, H, Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, 33612, USA.
Cell Commun Signal. 2010 Sep 22;8:27. doi: 10.1186/1478-811X-8-27.
In the last fifteen years, rapid progress has been made in delineating the cellular response to DNA damage. The DNA damage response network is composed of a large number of proteins with different functions that detect and signal the presence of DNA damage in order to coordinate DNA repair with a variety of cellular processes, notably cell cycle progression. This signal, which radiates from the chromatin template, is driven primarily by phosphorylation events, mainly on serine and threonine residues. While we have accumulated detailed information about kinases and their substrates our understanding of the role of phosphatases in the DNA damage response is still preliminary. Identifying the phosphatases and their regulation will be instrumental to obtain a complete picture of the dynamics of the DNA damage response. Here we give an overview of the DNA damage response in mammalian cells and then review the data on the role of different phosphatases and discuss their biological relevance.
在过去的十五年中,人们在描绘细胞对 DNA 损伤的反应方面取得了飞速的发展。DNA 损伤反应网络由大量具有不同功能的蛋白质组成,这些蛋白质能够检测和发出 DNA 损伤的存在信号,从而协调 DNA 修复与多种细胞过程,特别是细胞周期进程。这个信号主要由丝氨酸和苏氨酸残基上的磷酸化事件驱动,从染色质模板中辐射出来。虽然我们已经积累了关于激酶及其底物的详细信息,但我们对磷酸酶在 DNA 损伤反应中的作用的理解仍然是初步的。确定磷酸酶及其调控机制对于获得 DNA 损伤反应动力学的完整图像将是至关重要的。在这里,我们概述了哺乳动物细胞中的 DNA 损伤反应,然后回顾了不同磷酸酶作用的相关数据,并讨论了它们的生物学相关性。