Taleei Reza, Weinfeld Michael, Nikjoo Hooshang
Radiation Biophysics Group, Department of Oncology-Pathology, Karolinska Institutet, Stockholm SE 171 76, Sweden.
Radiat Prot Dosimetry. 2011 Feb;143(2-4):191-5. doi: 10.1093/rpd/ncq535. Epub 2010 Dec 23.
Ionising radiation induces different types of DNA damage, including single-strand breaks, double-strand breaks (DSB) and base damages. DSB are considered to be the most critical lesion to be repaired. The three main competitive pathways in the repair of DSB are non-homologous end joining (NHEJ), homologous recombination (HR) and single-strand annealing (SSA). SSA is a non-conservative repair pathway requiring direct repeat sequences for the repair process. In this work, a biochemical kinetic model is presented to describe the SSA repair pathway. The model consists of a system of non-linear ordinary differential equations describing the steps in the repair pathway. The reaction rates were estimated by comparing the model results with the experimental data for chicken DT40 cells exposed to 20 Gy of X-rays. The model successfully predicts the repair of the DT40 cells with the reaction rates derived from the 20-Gy X-ray experiment. The experimental data and the kinetic model show fast and slow DSB repair components. The half time and fractions of the slow and the fast components of the repair were compared for the model and the experiments. Mathematical and computational modelling in biology has played an important role in predicting biological mechanisms and stimulating future experimentation. The present model of SSA adds to the modelling of NHEJ and HR to provide a more complete description of DSB repair pathways.
电离辐射会引发不同类型的DNA损伤，包括单链断裂、双链断裂（DSB）和碱基损伤。双链断裂被认为是最需要修复的关键损伤。双链断裂修复的三个主要竞争途径是非同源末端连接（NHEJ）、同源重组（HR）和单链退火（SSA）。单链退火是一种非保守的修复途径，修复过程需要直接重复序列。在这项工作中，我们提出了一个生化动力学模型来描述单链退火修复途径。该模型由一个非线性常微分方程组组成，描述了修复途径中的各个步骤。通过将模型结果与暴露于20 Gy X射线的鸡DT40细胞的实验数据进行比较，估算了反应速率。该模型成功地利用从20 Gy X射线实验得出的反应速率预测了DT40细胞的修复情况。实验数据和动力学模型显示了双链断裂修复的快速和慢速成分。比较了模型和实验中修复的慢速和快速成分的半衰期及比例。生物学中的数学和计算建模在预测生物学机制和推动未来实验方面发挥了重要作用。目前的单链退火模型补充了非同源末端连接和同源重组的模型，以更完整地描述双链断裂修复途径。
