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Chromosoma. 2014 Mar;123(1-2):103-15. doi: 10.1007/s00412-013-0432-y. Epub 2013 Aug 28.

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

Author information

1
Institute for Theoretical Physics, Heidelberg University, Philosophenweg 19, 69120, Heidelberg, Germany, y.zhang@tphys.uni-heidelberg.de.

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.

PMID:
23982751
DOI:
10.1007/s00412-013-0432-y
[Indexed for MEDLINE]

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