A role for DNA-PK in retroviral DNA integration
A role for DNA-PK in retroviral DNA integration
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DOI：
10.1126/science.284.5414.644
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发表时间：
1999-04-23
期刊：
影响因子：
56.9
通讯作者：
Skalka, AM
中科院分区：
文献类型：
--
作者：
Daniel, R;Katz, RA;Skalka, AM
逆转录病毒 DNA 整合由病毒蛋白整合酶催化。这里表明，DNA依赖性蛋白激酶（DNA-PK）（一种宿主细胞蛋白）也参与该反应。 DNA-PK 缺陷的小鼠 scid 细胞感染三种不同的逆转录病毒后，逆转录病毒 DNA 整合显着减少，并因细胞凋亡而死亡。感染整合酶缺陷型病毒后未观察到 Scid 细胞杀伤作用。表明失败的整合是这些 DNA 修复缺陷细胞死亡的触发因素。这些结果表明，逆转录病毒整合的初始事件被宿主细胞检测为DNA损伤，并且整合过程的完成需要DNA-PK介导的修复途径。
Retroviral DNA integration is catalyzed by the viral protein integrase. Here, it is shown that DNA-dependent protein kinase (DNA-PK), a host cell protein, also participates in the reaction. DNA-PK-deficient murine scid cells infected with three different retroviruses showed a substantial reduction in retroviral DNA integration and died by apoptosis. Scid cell killing was not observed after infection with an integrase-defective virus. suggesting that abortive integration is the trigger for death in these DNA repair-deficient cells. These results suggest that the initial events in retroviral integration are detected as DNA damage by the host cell and that completion of;the integration process requires the DNA-PK-mediated repair pathway.