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首页> 外文期刊>Radiation Research: Official Organ of the Radiation Research Society >DEVELOPING A MODEL OF DNA REPLICATION TO BE USED FOR MONTE CARLO CALCULATIONS THAT PREDICT THE SIZES AND SHAPES OF MOLECULES RESULTING FROM DNA DOUBLE-STRAND BREAKS INDUCED BY X IRRADIATION DURING DNA SYNTHESIS
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DEVELOPING A MODEL OF DNA REPLICATION TO BE USED FOR MONTE CARLO CALCULATIONS THAT PREDICT THE SIZES AND SHAPES OF MOLECULES RESULTING FROM DNA DOUBLE-STRAND BREAKS INDUCED BY X IRRADIATION DURING DNA SYNTHESIS

机译：建立用于蒙特卡罗计算的DNA复制模型，该模型可预测DNA合成过程中X射线诱导的DNA双链断裂导致的分子大小和形状。

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A Monte Carlo computer program was written to introduce double-strand breaks (DSBs) randomly into cellular DNA that is configured according to different models of DNA replication. Then, from a review of the literature using DNA fiber autoradiography and other studies relating to rates of replication of DNA that is organized in similar to 3-Mbp regions or bands, a particular model for DNA replication was developed. Using this model, Monte Carlo calculations were made to predict the types and sizes of molecules that would result from introducing DSBs into DNA when synchronous cells are irradiated in the middle of S phase. Then results of the Monte Carlo calculations were compared with migration profiles obtained by pulsed-field gel electrophoresis (PFGE) for molecular size distributions of linear DNA molecules. For these comparisons, CHO cells irradiated in S phase also were pulse-labeled at the time of irradiation with [H-3]dThd for 15 min to compare the migration patterns of H-3-labeled replicating DNA with those of the mass of S-phase DNA, measured by imaging with a CCD camera. For the Monte Carlo calculations, we assumed from the reports in the literature that molecules containing replication bubbles with and without forks would be trapped in the PFGE plug. We also assumed that those molecules that are less than or equal to 8 Mbp, both linear and with replication forks, would be released into the lane. However, similar to 75% of the H-3-labeled DNA that is released from the plug migrated much more slowly than linear molecules, which we attributed to the slow migration of H-3-labeled molecules having replication forks not attached to bubbles. The percentages of both mass of S-phase DNA and H-3-labeled replicating DNA released from the plug, as determined by PFGE, were compared with comparable values determined from Monte Carlo calculations. A DNA replication model that provides good agreement between the PFGE results and Monte Carlo calculations is described. Furthermore, Monte Carlo methodology is presented that can be used for comparing data obtained with PFGE with results of Monte Carlo calculations that are based on different models of DNA replication and different assumptions for the migration of various types of replicating molecules. (C) 1997 by Radiation Research Society. [References: 61]
机译：编写了一个Monte Carlo计算机程序，将双链断裂（DSB）随机引入到细胞DNA中，该DNA根据不同的DNA复制模型进行配置。然后，从对使用DNA纤维放射自显影技术的文献的回顾以及与以类似于3-Mbp区域或条带的形式组织的DNA复制速率有关的其他研究中，发现了一种特定的DNA复制模型。使用该模型，进行了蒙特卡洛计算，以预测当在S相中间照射同步细胞时，将DSB引入DNA所产生的分子的类型和大小。然后将蒙特卡洛计算的结果与通过脉冲场凝胶电泳（PFGE）获得的线性DNA分子的分子大小分布的迁移曲线进行比较。为了进行这些比较，在用[H-3] dThd照射15分钟时，还对S期照射的CHO细胞进行了脉冲标记，以比较H-3标记的复制DNA和S量的迁移模式。相DNA，通过CCD相机成像测量。对于蒙特卡洛计算，我们从文献报告中假设，包含有和没有叉的复制气泡的分子将被困在PFGE塞子中。我们还假设线性或带有复制叉的小于或等于8 Mbp的分子将被释放到泳道中。然而，类似于从插塞释放的H-3标记的DNA中有75％的迁移比线性分子的迁移要慢得多，这归因于H-3标记的分子的复制叉未附着在气泡上的缓慢迁移。通过PFGE测定，从塞子释放的S期DNA和H-3标记的复制DNA的质量百分比与通过蒙特卡洛计算确定的可比值进行了比较。描述了一种DNA复制模型，该模型在PFGE结果与蒙特卡洛计算之间提供了良好的一致性。此外，提出了蒙特卡洛方法，可用于将PFGE获得的数据与基于不同DNA复制模型和不同类型复制分子迁移的不同假设的蒙特卡洛计算结果进行比较。 （C）1997年，辐射研究学会。 [参考：61]

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