1. Chromatin mobility is increased at sites of DNA double-strand breaks.
- Author
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Krawczyk PM, Borovski T, Stap J, Cijsouw T, ten Cate R, Medema JP, Kanaar R, Franken NA, and Aten JA
- Subjects
- Cell Line, Tumor, Cell Nucleus drug effects, Cell Nucleus genetics, Cell Nucleus radiation effects, Chromatin drug effects, Chromatin genetics, Chromatin radiation effects, Chromosome Aberrations drug effects, Chromosome Aberrations radiation effects, DNA Damage, Etoposide pharmacology, Fluorescence, Gamma Rays, Humans, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins metabolism, Models, Molecular, Motion, Plasmids, Staining and Labeling, Time-Lapse Imaging, Transfection, Tumor Suppressor p53-Binding Protein 1, Cell Nucleus metabolism, Chromatin metabolism, DNA Breaks, Double-Stranded drug effects, DNA Breaks, Double-Stranded radiation effects, DNA Repair genetics
- Abstract
DNA double-strand breaks (DSBs) can efficiently kill cancer cells, but they can also produce unwanted chromosome rearrangements when DNA ends from different DSBs are erroneously joined. Movement of DSB-containing chromatin domains might facilitate these DSB interactions and promote the formation of chromosome rearrangements. Therefore, we analyzed the mobility of chromatin domains containing DSBs, marked by the fluorescently tagged DSB marker 53BP1, in living mammalian cells and compared it with the mobility of undamaged chromatin on a time-scale relevant for DSB repair. We found that chromatin domains containing DSBs are substantially more mobile than intact chromatin, and are capable of roaming a more than twofold larger area of the cell nucleus. Moreover, this increased DSB mobility, but not the mobility of undamaged chromatin, can be reduced by agents that affect higher-order chromatin organization.
- Published
- 2012
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