Yuan Zhigang, Seto Edward
H. Lee Moffitt Cancer Center and Research Institute; Tampa, Florida 33612, USA.
Cell Cycle. 2007 Dec 1;6(23):2869-71. doi: 10.4161/cc.6.23.5026.
In mammalian cells, DNA is often subjected to stresses such as ionizing radiation (IR) that can induce DNA double strand breaks (DSBs). In response to DNA DSBs, mammalian cells activate a rapid phosphorylation signaling cascade through the protein kinases, Ataxia-Telangiectasia Mutated (ATM) and ATM- and Rad3-Related (ATR). Many well-characterized DNA repair factors are phosphorylated by ATM in response to DSBs, and the sequential phosphorylation of some of these factors, including NBS1, delay cell cycle progression (checkpoint arrest) to allow time for DNA damage repair. Results from a new study suggest that phosphorylation of NBS1 is regulated by the acetylation status of the protein, which is modulated by SIRT1 deacetylase.
在哺乳动物细胞中，DNA常常会受到诸如电离辐射（IR）等应激因素的影响，这些因素可诱导DNA双链断裂（DSB）。作为对DNA双链断裂的响应，哺乳动物细胞通过蛋白激酶共济失调毛细血管扩张突变蛋白（ATM）和ATM及Rad3相关蛋白（ATR）激活快速磷酸化信号级联反应。许多已得到充分表征的DNA修复因子会在DNA双链断裂时被ATM磷酸化，其中一些因子（包括NBS1）的顺序磷酸化会延迟细胞周期进程（检查点停滞），以便有时间进行DNA损伤修复。一项新研究的结果表明，NBS1的磷酸化受该蛋白乙酰化状态的调控，而这种状态由SIRT1脱乙酰酶调节。
