DNA double-strand breaks: linking gene expression to chromosome morphology and mobility

Ionizing radiation can lead to DNA double-strand breaks (DSBs) which belong to the most dangerous forms of damage to the DNA. Cells possess elaborate repair mechanisms and react in a complex manner to the emergence of DSBs. Experiments have shown that gene expression levels in irradiated cells are changed, and thousands of radiation-responsive genes have been identified. On the other hand, recent studies have shown that gene expression is tightly connected to the three-dimensional organization of the genome. In this work, we analyzed the chromatin organization in the cell nuclei before and after exposure to ionizing radiation with an expression-dependent folding model. Our results indicate that the alteration of the chromosome organization on the scale of a complete chromosome is rather limited despite the expression level change of a large number of genes. We further modelled breaks within sub-compartments of the model chromosomes and showed that entropic changes caused by a break lead to increased mobility of the break sites and help to locate break ends further to the periphery of the sub-compartments. We conclude that the changes in the chromatin structure after irradiation are limited to local scales and demonstrate the importance of entropy for the behaviour of break ends.