细菌在面对碳源、氮源饥饿等的压力时，会发生严紧反应，导致DNA复制停止，但其调控机制还不完全清楚。我们利用蛋白质组学技术发现细菌中存在广泛的蛋白质乙酰化修饰现象， 其中控制着DNA复制起始的DnaA存在乙酰化修饰，且在碳源饥饿的压力下，胞质DnaA不仅乙酰化水平升高，而且含量显著降低，存在降解现象。我们提出假说：在碳源、氮源饥饿等压力状况下，大肠埃希菌通过调节DnaA的乙酰化修饰来降低DnaA的稳定性，迅速降低胞质DnaA浓度，从而阻止DNA的复制起始，抑制细菌分裂。因此本课题拟采用体内和体外研究策略与方法，探索DnaA乙酰化修饰与其稳定性的关系，研究DNA复制起始调控的机制，深入理解严紧反应过程中DNA的调控，为揭示细菌应对外界压力的自我保护机制提供新的视角。

When bacteria encounter environmental stresses, for example starvation condition, the stringent response is activated, and DNA replication is halted. Whereas the underlying mechanisms remain unclear. We found that many bacterial proteins were acetylated by proteomics and the acetylation regulated their functions. DnaA controls the initiation of bacterial DNA replication. We found that DnaA was acetylated in Escherichia coli . The acetylation level of DnaA increased and meanwhile the stability of DnaA decreased under carbon starvation. We hypothesized that bacteria could decrease the stability of DnaA by increasing the acetylation level of DnaA under the conditions of carbon or nitrogen starvation. By this mean, cells can promptly decrease the concentration of DnaA and stop DNA replication initiation as well as cell division. Therefore, we will study the relationship between the acetylation of DnaA and the stability of DnaA in vitro and in vivo. We will find whether the acetylation of DnaA regulates the stability of DnaA and how it regulates, especially under the condition of stringent response. Our study will reveal the new regulation mechanism of DNA replication initiation and understand how DNA replication is regulated during the stringent response. The information derived from this project will provide a new perspective for better understanding mechanisms of bacteria’s self-protection against such stresses.