Chromatin structure influences the sensitivity of DNA to gamma-radiation

Biochimica Et Biophysica Acta
Martin FalkStanislav Kozubek

Abstract

For the first time, DNA double-strand breaks (DSBs) were directly visualized in functionally and structurally different chromatin domains of human cells. The results show that genetically inactive condensed chromatin is much less susceptible to DSB induction by gamma-rays than expressed, decondensed domains. Higher sensitivity of open chromatin for DNA damage was accompanied by more efficient DSB repair. These findings follow from comparing DSB induction and repair in two 11 Mbp-long chromatin regions, one with clusters of highly expressed genes and the other, gene-poor, containing mainly genes having only low transcriptional activity. The same conclusions result from experiments with whole chromosome territories, differing in gene density and consequently in chromatin condensation. It follows from our further results that this lower sensitivity of DNA to the damage by ionizing radiation in heterochromatin is not caused by the simple chromatin condensation but very probably by the presence of a higher amount of proteins compared to genetically active and decondensed chromatin. In addition, our results show that some agents potentially used for cell killing in cancer therapy (TSA, hypotonic and hypertonic) influence cell surviva...Continue Reading

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Citations

Feb 19, 2013·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Lucie JežkováStanislav Kozubek
Mar 5, 2013·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Martin FalkStanislav Kozubek
Sep 21, 2013·DNA Repair·Mario Moscariello, George Iliakis
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Mar 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Donglai WangWei-Guo Zhu
May 24, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Igor KoturbashIgor P Pogribny
Feb 18, 2011·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Kendra L Cann, Graham Dellaire
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Oct 17, 2013·PloS One·Hideaki TakataKazuhiro Maeshima
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May 3, 2016·Mutation Research·Peter Lenart, Lumir Krejci
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