Random breakage and reunion chromosome aberration formation model; an interaction-distance version based on chromatin geometry.
Random breakage and reunion chromosome aberration formation model; an interaction-distance version based on chromatin geometry.
复制标题
随机断裂与团聚染色体畸变形成模型；
DOI：
10.1080/09553000050201064
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发表时间：
2000
影响因子：
2.6
通讯作者：
Hlatky,LR
中科院分区：
文献类型：
--
作者：
Sachs,RK;Levy,D;Chen,AM;Simpson,PJ;Cornforth,MN;Ingerman,EA;Hahnfeldt,P;Hlatky,LR
目的利用已发表的人成纤维细胞染色体畸变的荧光原位杂交（FISH）数据，检验一个断裂-再结合模型，该模型假设DNA双链断裂（DSB）自由末端的两两错接，除了邻近效应外是随机的。CAS（染色体畸变模拟器）Monte Carlo计算机软件实现的模型进行了修改，使用的距离算法，而不是使用DSB相互作用的网站。修改（称为CAS 2）允许一个更现实的方法来大规模的染色质几何形状，染色体领土和邻近效应。结果CAS 2的结果优于CAS 2，但与CAS 2相比，CAS 2的结果更接近于CAS 2。一个合理的拟合与几个差异，获得了在三个不同的辐射剂量的许多不同的畸变类型和畸变涉及各种特定的染色体在一个大的数据集，使用一个油漆FISH评分的频率。最佳平均染色体区域交叉因子为~1.1，表明对于细胞核中任意选择的位置，平均略多于两条染色体具有非常接近的基因座。在不改变这三个参数值，也得到了相应的，较小的，两个油漆dataset.ConclusionsA随机断裂和团聚模型，采用距离算法的邻近效应得到了可接受的近似硬X射线像差模式的许多细节。然而，发现了足够的差异，仍然存在额外或替代形成机制的可能性。
PurposeUsing published FISH data for chromosome aberration production in human fibroblasts by hard X-rays to test a breakage-and-reunion model.MethodsThe model assumed pairwise misrejoining, random apart from proximity e ffects, of DNA double-strand break (DSB) free ends. CAS (chromosome aberration simulator) Monte Carlo computer software implementing the model was modified to use a distance algorithm for misrejoining instead of using DSB interaction sites. The modification (called CAS2) allowed a somewhat more realistic approach to large-scale chromatin geometry, chromosome territories and proximity effects. It required adding a third adjustable parameter, the chromosome territory intersection factor, quantifying the amount of intertwining among different chromosomes.ResultsCAS2 gave somewhat better results than CAS. A reasonable fit with a few discrepancies was obtained for the frequencies at three different radiation doses of many different aberration types and of aberrations involving various specific chromosomes in a large data set using one-paint FISH scoring. The optimal average chromosome territory intersection factor was ~1.1, indicating that, for an arbitrarily chosen location in the nucleus, on average slightly more than two chromosomes have very nearby loci. Without changing the three parameter values, a fit was also obtained for a corresponding, smaller, two-paint data set.ConclusionsA random breakage-and-reunion model incorporating proximity effects by using a distance algorithm gave acceptable approximations for many details of hard X-ray aberration patterns. However, enough discrepancies were found that the possibility of an additional or alternate formation mechanism remains.