Wu Wenlei, Sun Weibin, Sun Tingzhe
* Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, Jiangsu 210008, P. R. China.
† School of Life Sciences, AnQing Normal University, AnQing, Anhui 246011, P. R. China.
J Bioinform Comput Biol. 2016 Feb;14(1):1650001. doi: 10.1142/S0219720016500013. Epub 2015 Sep 16.
The tumor suppressor p53 can be activated by DNA damage and exhibits undamped pulses. Recent reports have demonstrated a non-threshold mechanism for p53 dynamics. However, no related theoretical studies have been proposed. Here, we constructed a refined DNA damage repair model that incorporated both intrinsic and extrinsic DNA lesions. We proposed that the basal DNA damage may trigger significant fractions of p53 pulses. We also reproduced the heterogeneity of p53 dynamics in experiments. The number of p53 pulses showed no correlations with DNA damage. We also replicated the linear correlation between DNA damage and the probability of igniting a pulse. Our model has unraveled the heterogeneous p53 responses.
肿瘤抑制因子p53可被DNA损伤激活并呈现无衰减脉冲。最近的报道证明了p53动力学的非阈值机制。然而,尚未有相关的理论研究被提出。在此,我们构建了一个完善的DNA损伤修复模型,该模型纳入了内在和外在的DNA损伤。我们提出基础DNA损伤可能触发相当一部分p53脉冲。我们还在实验中重现了p53动力学的异质性。p53脉冲的数量与DNA损伤无关。我们还复制了DNA损伤与引发脉冲概率之间的线性相关性。我们的模型揭示了p53的异质性反应。