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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 significance in studying the function of the cell cycle, regulatory mechanism, and relationships among the proteins involved in the regulation in biological engineering and other fields. 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 suffers 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.
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Keywords:
- DNA damage /
- protein network /
- self-repairing /
- cell cycle regulatory
[1] Wang Y 2010 Ph. D. Dissertation (Haerbin: Haerbin University of Technology) (in Chinese) [王印 2010 博士学位论文(哈尔滨: 哈尔滨工业大学)]
[2] Ji C, Zhang L Y, Dou S X, Wang P Y 2011 Acta Phys. Sin. 60 098703 (in Chinese) [季超, 张凌云, 窦硕星, 王鹏业 2011 60 098703]
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[5] Liu H 2009 Ph. D. Dissertation (Tianjin: Hebei University of Technology) (in Chinese) [柳辉 2009 博士学位论文(天津: 河北工业大学)]
[6] Song Q, Cao J D, Liu F 2010 Phys. Lett. A 374 544
[7] Selivanov A A, Lehnert J, Dahms T, Hövel P, Fradkov A L, Schöll E 2012 Phys. Rev. E 85 016201
[8] Chen D B, L L Y, Shang M S, Zhang Y C, Zhou T 2011 Physica A 391 1777
[9] Zhang F Y, Zhang J Z, Zou S B, Cheng Z F, Cai Y, Xuan Y H 2011 J. Clin. Exp. Pathol. 54 5104 (in Chinese) [张凤艳, 张金子, 邹树彪, 程志芬, 才勇, 玄延花 2011 临床与实验病理学杂志 54 5104]
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[11] Gui M Q, Lin G 2010 Math. Comput. Model 52 2066
[12] Zhou T, Zou S R, Gu A H, Wei L, Xu Y Y 2009 Sci. & Technol. Inf. 35 82 (in Chinese) [周塔, 邹盛荣, 顾爱华, 卫丽, 徐莹莹 2009 科技信息 35 82]
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[14] Yu Z G, Xiao Q J, Shi L, Yu J W, Vo Anh 2010 Chin. Phys. B 19 068701
[15] Pan Y, Feng Z N, Diao Y B 2007 Comput. Apl. Chem. 24 56 (in Chinese) [潘义, 冯子男, 刁元波 2007 计算机与应用化学 24 56]
[16] Gao J, Jiang L L, Xu Z Y 2009 Chin. Phys. B 18 4571
[17] Sun T T, Ma H Z, Jiang Z T 2012 Chin. Phys. B 21 038702
[18] Newman M E J 2003 SIAM Rev. 45 167
[19] Albert R, BarabasiA L 2002 Rev. Mod. Phys. 74 47
[20] Watts D J, Strogatz S H 1998 Nat. 393 440
[21] Barabasi A L, Albert R 1999 Sci. 286 509
[22] Dai R W, Cao L B 2001 J. Syst. Eng. 16 376 (in Chinese) [戴汝为, 操龙兵 2001 系统工程学报 16 376]
[23] Chi L P, Cai X 2003 Chin. Phys. Lett. 20 1393
[24] Wan Q, Zhou J, Liu Z R 2012 Acta Phys. Sin. 61 010203 (in Chinese) [万茜, 周进, 刘曾荣 2012 61 010203]
[25] Li Z Q, Zhang R X, Yang Z, Zhao H Z, Yu J H 2012 Acta Phys. Sin. 61 238902 (in Chinese) [李泽荃, 张瑞新, 杨曌, 赵红泽, 于健浩 2012 61 238902]
[26] Zhang W Q 2010 Ph. D. Dissertation (Beijing: PLA Military Academy of Medical Sciences) (in Chinese) [张万巧 2010 博士学位论文(北京: 中国人民解放军军事医学科学院)]
[27] Gao L F, Shi J J, Guan S 2010 Chin. Phys. B 19 010512
[28] Donjerkovic D, Scott D W 2000 Cel. Res. 10 1
[29] Sheaff R J, Groudine M, Gordon M, Roberts J M, Clurman B E 1997 Genes Dev. 11 1464
[30] Ye W M, Lv B B, Zhao C, Di Z R 2013 Acta Phys. Sin. 62 010507 (in Chinese) [叶纬明, 吕彬彬, 赵琛, 狄增如 2013 62 010507]
[31] Pellegata N S, Antoniono R J, Redpath J L, Stanbridge E J 1996 Proceeding of The National Academy of Science USA 1996 p15209
[32] Lev Bar-Or R, Maya R, Lee A S, Uri A, Arnold J L, Moshe O 2000 Proceeding of The National Academy of Science USA 2000 p11250
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[1] Wang Y 2010 Ph. D. Dissertation (Haerbin: Haerbin University of Technology) (in Chinese) [王印 2010 博士学位论文(哈尔滨: 哈尔滨工业大学)]
[2] Ji C, Zhang L Y, Dou S X, Wang P Y 2011 Acta Phys. Sin. 60 098703 (in Chinese) [季超, 张凌云, 窦硕星, 王鹏业 2011 60 098703]
[3] Shang Y, Chen M Y, Kurths J 2009 Phys. Rev. E 80 027201
[4] Zhu P, Tang X Q, Xu Z Y 2009 Chin. Phys. B 18 363
[5] Liu H 2009 Ph. D. Dissertation (Tianjin: Hebei University of Technology) (in Chinese) [柳辉 2009 博士学位论文(天津: 河北工业大学)]
[6] Song Q, Cao J D, Liu F 2010 Phys. Lett. A 374 544
[7] Selivanov A A, Lehnert J, Dahms T, Hövel P, Fradkov A L, Schöll E 2012 Phys. Rev. E 85 016201
[8] Chen D B, L L Y, Shang M S, Zhang Y C, Zhou T 2011 Physica A 391 1777
[9] Zhang F Y, Zhang J Z, Zou S B, Cheng Z F, Cai Y, Xuan Y H 2011 J. Clin. Exp. Pathol. 54 5104 (in Chinese) [张凤艳, 张金子, 邹树彪, 程志芬, 才勇, 玄延花 2011 临床与实验病理学杂志 54 5104]
[10] Ding D W 2012 Comput. Apl. Chem. 29 347 (in Chinese) [丁德武 2012 计算机与应用化学 29 347]
[11] Gui M Q, Lin G 2010 Math. Comput. Model 52 2066
[12] Zhou T, Zou S R, Gu A H, Wei L, Xu Y Y 2009 Sci. & Technol. Inf. 35 82 (in Chinese) [周塔, 邹盛荣, 顾爱华, 卫丽, 徐莹莹 2009 科技信息 35 82]
[13] Zhang L J, Yan S W, Zhuo Y Z 2007 Chin. Phys. Sin. 56 2442 (in Chinese) [张丽娟, 晏世伟, 卓益忠 2007 56 2442]
[14] Yu Z G, Xiao Q J, Shi L, Yu J W, Vo Anh 2010 Chin. Phys. B 19 068701
[15] Pan Y, Feng Z N, Diao Y B 2007 Comput. Apl. Chem. 24 56 (in Chinese) [潘义, 冯子男, 刁元波 2007 计算机与应用化学 24 56]
[16] Gao J, Jiang L L, Xu Z Y 2009 Chin. Phys. B 18 4571
[17] Sun T T, Ma H Z, Jiang Z T 2012 Chin. Phys. B 21 038702
[18] Newman M E J 2003 SIAM Rev. 45 167
[19] Albert R, BarabasiA L 2002 Rev. Mod. Phys. 74 47
[20] Watts D J, Strogatz S H 1998 Nat. 393 440
[21] Barabasi A L, Albert R 1999 Sci. 286 509
[22] Dai R W, Cao L B 2001 J. Syst. Eng. 16 376 (in Chinese) [戴汝为, 操龙兵 2001 系统工程学报 16 376]
[23] Chi L P, Cai X 2003 Chin. Phys. Lett. 20 1393
[24] Wan Q, Zhou J, Liu Z R 2012 Acta Phys. Sin. 61 010203 (in Chinese) [万茜, 周进, 刘曾荣 2012 61 010203]
[25] Li Z Q, Zhang R X, Yang Z, Zhao H Z, Yu J H 2012 Acta Phys. Sin. 61 238902 (in Chinese) [李泽荃, 张瑞新, 杨曌, 赵红泽, 于健浩 2012 61 238902]
[26] Zhang W Q 2010 Ph. D. Dissertation (Beijing: PLA Military Academy of Medical Sciences) (in Chinese) [张万巧 2010 博士学位论文(北京: 中国人民解放军军事医学科学院)]
[27] Gao L F, Shi J J, Guan S 2010 Chin. Phys. B 19 010512
[28] Donjerkovic D, Scott D W 2000 Cel. Res. 10 1
[29] Sheaff R J, Groudine M, Gordon M, Roberts J M, Clurman B E 1997 Genes Dev. 11 1464
[30] Ye W M, Lv B B, Zhao C, Di Z R 2013 Acta Phys. Sin. 62 010507 (in Chinese) [叶纬明, 吕彬彬, 赵琛, 狄增如 2013 62 010507]
[31] Pellegata N S, Antoniono R J, Redpath J L, Stanbridge E J 1996 Proceeding of The National Academy of Science USA 1996 p15209
[32] Lev Bar-Or R, Maya R, Lee A S, Uri A, Arnold J L, Moshe O 2000 Proceeding of The National Academy of Science USA 2000 p11250
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