Competition effect in DNA damage response
Competition effect in DNA damage response
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DOI：
10.1007/s00411-008-0182-z
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发表时间：
2008-11-01
影响因子：
1.7
通讯作者：
Friedl, Anna A.
中科院分区：
文献类型：
--
作者：
Greubel, Christoph;Hable, Volker;Friedl, Anna A.
我们已经建立了一个离子微束，用于在单细胞水平上研究核形貌和双链断裂修复动力学。在这里，我们表明，第一次和第二次延迟单离子暴露在不同的核位点导致磷酸化- atm， γ - h2ax和Mdc1在较早(e)和较晚(l)微辐照位点的积累相当。相反，53BP1和重组蛋白Rad51在l位点的积累明显减少。这种明显的竞争效应伴随着辐照核未损伤区域53BP1的减少。我们认为，一个极其有限的池大小，加上在辐照位点的强结合，导致在核空间自由漫游的未结合因子耗尽。这些因子在l位点的供应不足还需要在e位点上长期结合或在l位点上较弱的结合。观察到的效应表明，单个核位点的DNA损伤反应取决于损伤负荷的时间过程。这可能对放射治疗有启示。
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.