1. Competition effect in DNA damage response.
- Author
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Greubel C, Hable V, Drexler GA, Hauptner A, Dietzel S, Strickfaden H, Baur I, Krücken R, Cremer T, Dollinger G, and Friedl AA
- Subjects
- DNA ultrastructure, Dose-Response Relationship, Radiation, Humans, Radiation Dosage, DNA radiation effects, DNA Damage physiology, DNA Repair physiology, DNA Repair radiation effects, Microscopy, Fluorescence methods
- Abstract
We have built an ion-microbeam for studies of the nuclear topography and kinetics of double-strand break repair at the single cell level. Here, we show that a first and a second, delayed single ion exposure at different nuclear sites led to comparable accumulations of phospho-ATM, gamma-H2AX and Mdc1 at both earlier (e) and later (l) microirradiated sites. In contrast, accumulations of 53BP1 and the recombination protein Rad51 were strongly reduced at l-sites. This apparent competition effect is accompanied by a reduced amount of 53BP1 in undamaged areas of the irradiated nuclei. We suggest that a critically limited pool size combined with strong binding at irradiated sites leads to the exhaustion of unbound factors freely roaming the nuclear space. The undersupply of these factors at l-sites requires in addition a long-lasting binding at e-sites or a weaker binding at l-sites. The observed effects suggest that DNA damage response at individual nuclear sites depends on the time course of damage load. This may have implications for therapeutic radiation treatments.
- Published
- 2008
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