Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015-Lausanne, Switzerland.
Nucleic Acids Res. 2013 Aug;41(14):6808-15. doi: 10.1093/nar/gkt480. Epub 2013 Jun 5.
Using numerical simulations of pairs of long polymeric chains confined in microscopic cylinders, we investigate consequences of double-strand DNA breaks occurring in independent topological domains, such as these constituting bacterial chromosomes. Our simulations show a transition between segregated and mixed state upon linearization of one of the modelled topological domains. Our results explain how chromosomal organization into topological domains can fulfil two opposite conditions: (i) effectively repulse various loops from each other thus promoting chromosome separation and (ii) permit local DNA intermingling when one or more loops are broken and need to be repaired in a process that requires homology search between broken ends and their homologous sequences in closely positioned sister chromatid.
利用长链聚合物对在微观圆柱内受限的双体模拟,我们研究了独立拓扑区域(如构成细菌染色体的区域)中双链 DNA 断裂的后果。我们的模拟表明,在对其中一个模拟拓扑区域进行线性化处理时,会发生从分离状态到混合状态的转变。我们的结果解释了染色体组织成拓扑区域如何能满足两个相反的条件:(i)有效地将各种环相互排斥,从而促进染色体分离;(ii)当一个或多个环断裂且需要在同源性搜索断裂末端与其在紧密定位的姐妹染色单体中的同源序列的过程中进行修复时,允许局部 DNA 混合。