基于DNA损伤的蛋白调控网络研究

Study on regulatory network of proteins based on DNA damage

细胞生长的每个阶段都离不开蛋白质相互作用.研究细胞周期的功能、调控机理及参与调控的蛋白质之间的关系对生物工程等领域有重大的应用价值.本文通过研究电离辐射下生物体细胞的DNA损伤后,细胞内以p53为核心的扩展蛋白调控网络的功能、原理及其自修复机理,在现有蛋白网络基础上引入更多蛋白网络调控因子来建立蛋白调控网络,仿真模拟更为全面的细胞周期进程;并且从复杂网络图论和细胞周期调控两个方面分析扩展PMP调控网络的抗扰能力及自修复机理,结果表明:1)蛋白网络在对抗环境中出现的小扰动时具有较强的稳定性.但在面对蓄意攻击时网络的稳定性较差.2)受损的DNA能否被修复取决于p53蛋白的动力学行为,即低损伤与中损伤情况下,p53可诱导细胞周期进程阻滞来完成细胞的自修复;而当高损伤或过损伤时,p53蛋白浓度表现为周期振荡行为并诱导细胞凋亡.

Each stage of cell growth is inseparable from the protein-protein interactions.It is of great signifcance in studying the function of the cell cycle,regulatory mechanism,and relationships among the proteins involved in the regulation in biological engineering and other felds.This paper studies the function,principle,and self-repairing mechanisms based on the intracellular protein p53 when DNA is damaged by ionizing radiation.We introduce more regulating factors for the proteins to build the networks based on the existing one and simulate a more comprehensive cell cycle progression.Then we analyze the anti-interference and self-repairing system of the regulatory networks using the complex network theory and cell cycle regulation.Numerical simulation results and experimental data show：（1） The protein network shows a stable condition when it sufers a small disturbance,while it shows a poor stability when facing deliberate attack;（2） whether the damaged DNA can be repaired depends on the dynamic behavior of p53 protein,i.e.,p53 can transmit the damage signal to the cell cycle regulatory factors through the signal transduction pathway to induce the cell cycle arrest so as to complete the self-repairing processes in the case of the low-damage and the medium-damage.When DNA comes to face the high-damage and the excess-damage,the concentration of p53 shows a periodic oscillation behavior and it can induce apoptosis.