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

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Abstract

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.

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Acknowledgments

We would like to thank Frederik Wenz, Jürgen Hesser, Carsten Herskind, Michael Hausmann and Hansjörg Jerabek for the fruitful discussions. YZ gratefully appreciates funding from the German National Academic Foundation (Studienstiftung des Deutschen Volkes) and support from the Heidelberg Graduate School for Mathematical and Computational Methods in the Sciences (HGS MathComp). Computer simulations were performed on bwGRiD (http://www.bw-grid.de), member of the German D-Grid initiative, funded by the Ministry for Education and Research (Bundesministerium für Bildung und Forschung) and the Ministry for Science, Research and Arts Baden-Wuerttemberg (Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg).

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The authors declare that they have no conflict of interest.

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  1. Institute for Theoretical Physics, Heidelberg University, Philosophenweg 19, 69120, Heidelberg, Germany

    Yang Zhang & Dieter W. Heermann

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  1. Yang Zhang
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Correspondence to Yang Zhang.

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Zhang, Y., Heermann, D.W. DNA double-strand breaks: linking gene expression to chromosome morphology and mobility. Chromosoma 123, 103–115 (2014). https://doi.org/10.1007/s00412-013-0432-y

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