Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Trends Biochem Sci. 2011 Nov;36(11):569-77. doi: 10.1016/j.tibs.2011.08.007. Epub 2011 Sep 18.
DNA-damage-induced phospho-signaling has been studied for decades, with a focus mainly on initiation of the signaling cascade, and the kinases activated by DNA lesions. It is widely accepted that the balance of phosphorylation needs to be restored and/or maintained by phosphatases, yet there have only been sporadic efforts to investigate the impact of phosphatases on DNA repair. Recent advances in phosphoproteomic strategies and implementation of large genetic screens indicate that these enzymes play pivotal roles in these signaling networks. Dephosphorylation of repair proteins is crucial for efficient DNA repair, and the recommencement of cell division post-repair. Here, we focus on serine/threonine phosphatases implicated in dephosphorylation of DNA repair factors, summarizing recent findings and speculating on untested roles of phosphatases in the DNA damage response.
DNA 损伤诱导的磷酸化信号转导已经研究了几十年,主要集中在信号级联的启动以及 DNA 损伤激活的激酶上。人们普遍认为,磷酸酶需要恢复和/或维持磷酸化的平衡,但只有零星的努力来研究磷酸酶对 DNA 修复的影响。磷酸化蛋白质组学策略的最新进展和大规模遗传筛选的实施表明,这些酶在这些信号网络中发挥着关键作用。修复蛋白的去磷酸化对于有效的 DNA 修复和修复后细胞分裂的重新开始至关重要。在这里,我们重点关注涉及 DNA 修复因子去磷酸化的丝氨酸/苏氨酸磷酸酶,总结最近的发现,并推测磷酸酶在 DNA 损伤反应中未被测试的作用。