Polymerase β Limits the Rate of DNA Single-Strand Break Repair

E.M. Pozdnyakov, A. Korneichuk, A. V. Rogacheva, G. Vasilev
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Abstract

Breaks that appear in DNA and violate its integrity are a serious threat to the life of the cell. There is a special repair system for their recovery, which includes many different enzymes. However, the exact mechanisms of this process are currently still unclear. In this article, we considered single-strand discontinuities based on the Michaelis–Menten equation and using the quasi-equilibrium approximation. A scheme of interaction between the mechanisms of the reparation system was developed and a computational model was built in the COPASI software to verify it. As a result of the work, the dependences of the concentrations of the participants in the repair system were obtained, and the known experimental data were also approximated. We observed that the plot with a logarithmic scale of fully corrected DNA concentration versus time is close to a sigmoid. We obtained that, the polymerase enzymatic reaction is the limiting factor for the rate of DNA repair and the rate of ligase operation is limited by the rate of DNA appearance. Being a regulatory link in the DNA repair system, polymerase and its parameters exert a control influence on the rest of the model parameters. In turn, the parameters for PARP1, PNKP, and LIG3α should provide rates of enzymatic reactions higher than the rate of polymerase operation.
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聚合酶β限制DNA单链断裂修复的速率
DNA中出现断裂并破坏其完整性是对细胞生命的严重威胁。它们的恢复有一个特殊的修复系统,其中包括许多不同的酶。然而,这一过程的确切机制目前仍不清楚。在本文中,我们基于Michaelis-Menten方程和准平衡近似考虑单链不连续。提出了一种补偿系统各机制间相互作用的方案,并在COPASI软件中建立了计算模型进行验证。得到了修复系统中各组分浓度的依赖关系,并对已知的实验数据进行了近似。我们观察到,具有完全校正的DNA浓度随时间的对数尺度的图接近于s形。我们发现,聚合酶的酶促反应是DNA修复速率的限制因素,连接酶的操作速率受DNA出现速率的限制。作为DNA修复系统中的调控环节,聚合酶及其参数对其余模型参数具有控制性影响。反过来,PARP1、PNKP和LIG3α的参数应该提供高于聚合酶操作速率的酶促反应速率。
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来源期刊
Mathematical Biology and Bioinformatics
Mathematical Biology and Bioinformatics Mathematics-Applied Mathematics
CiteScore
1.10
自引率
0.00%
发文量
13
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