期刊
RADIATION AND ENVIRONMENTAL BIOPHYSICS
卷 47, 期 4, 页码 423-429出版社
SPRINGER
DOI: 10.1007/s00411-008-0182-z
关键词
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资金
- European Science Foundation (ESF) under the EUROCORES Programme EuroDYNA (G.D., T.C., A.A.F.)
- DFG Cluster of Excellence Munich Centre for Advanced Photonics (G.D., A.A.F.)
- Bundesamt fur Strahlenschutz (A.A.F.)
- Bundesministerium fur Bildung und Forschung (A.A.F.).
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.
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