Ionizing radiation enhances double-strand-break repair in rapamycin-treated ataxia telangiectasia lymphoblasts.
Ionizing radiation enhances double-strand-break repair in rapamycin-treated ataxia telangiectasia lymphoblasts.
复制标题
电离辐射增强雷帕霉素治疗的共济失调毛细血管扩张淋巴母细胞的双链断裂修复。
DOI：
10.1080/095530000138835
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发表时间：
2000
影响因子：
2.6
通讯作者：
Wang,Y
中科院分区：
文献类型：
--
作者：
Sikpi,MO;Wang,Y
PurposeUnlike normal cells, ataxia telangiectasia (A-T) cells do not exhibit enhanced double-strand-break (dsb)-repair fidelity after ionizing radiation (IR) exposure. DNA-repair induction and other responses to IR are mediated by signalling pathways that are defective in A-T cells. Ataxia telangiectasia mutated (ATM) protein, the mutated protein in A-T cells, is homologous to members of the P13-kinase, including the rapamycin target FRAP. Rapamycin kills normal cells more readily in normal than in A-T cells, and inhibits the FRAP target p70 S6 kinase (p70 S6K) more readily in normal than in A-T cells. Also, PHAS-1, another FRAP target, may also be a substrate for ATM. Because ATM plays a role in the response of mammalian cells to rapamycin, the effect of rapamycin on IR enhancement of dsb repair was investigated.Materials and methodsDouble-strand-break repair by normal and A-T lymphoblasts, either untreated or treated with rapamycin and gamma-irradiated, was analysed using shuttle pZ189 containing a dsb.ResultsDouble-strand-break-rejoining fidelity in linear plasmids (linDNA) processed in either untreated or rapamycin-treated normal cells increased about twofold if transfection occurred immediately after host irradiation. In contrast, radiation did not increase or decrease the repair fidelity by untreated A-T host cells. But, like normal hosts, dsb-repair fidelity improved twofold in A-T hosts treated with rapamycin. Treatment with the P13-kinase inhibitor LY294002 did not alter dsb-rejoining fidelity in normal or in A-T hosts.ConclusionsThese findings demonstrate that rapamycin does not affect IR enhancement of dsb-repair fidelity in normal cells but restores this phenomenon in A-T lymphoblasts, and suggests the involvement of a rapamycin-sensitive pathway in radiation-enhanced dsb repair.
