Increased sensitivity of DNA damage response-deficient cells to stimulated microgravity-induced DNA lesions.
Increased sensitivity of DNA damage response-deficient cells to stimulated microgravity-induced DNA lesions.
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DNA 损伤反应缺陷细胞对刺激微重力诱导的 DNA 损伤的敏感性增加
DOI：
10.1371/journal.pone.0125236
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hang H
中科院分区：
文献类型：
--
作者：
Li N;An L;Hang H
微重力是宇航员在太空中必须面对的一个主要压力因素。在过去，研究了微重力对基因组DNA损伤的影响，似乎对基因组DNA的影响取决于细胞类型和暴露于微重力或模拟微重力（SMG）的时间长度。在这项研究中，我们使用小鼠胚胎干细胞（MES）和小鼠胚胎成纤维细胞（MEF）细胞来评估SMG对DNA损伤的影响。为了深入了解细胞抵抗和/或适应SMG的潜在机制，我们在本研究中除了野生型细胞之外还包括Rad 9缺失的MES和Mdc 1缺失的MEF细胞。我们在Rad 9-/- MES和Mdc 1-/- MEF细胞中观察到显著的SMG诱导的DNA双链断裂（DSB），但在其相应的野生型细胞中没有观察到。在Rad 9-/- MES中也观察到类似的DNA单链断裂或修饰模式。随着SMG暴露时间的延长，Rad 9-/- MES细胞通过减少诱导的DNA损伤来适应SMG干扰。在Rad 9-/- MES中诱导的DNA损伤是由于SMG诱导的活性氧（ROS）。有趣的是，Mdc 1-/- MEF细胞仅部分适应SMG干扰。也就是说，诱导的DNA损伤随时间减少，但没有恢复到对照水平，而ROS恢复到对照水平。另外，ROS对Mdc 1-/- MEF细胞DNA损伤的作用仅部分起作用。综上所述，这些数据表明SMG是一种弱的基因组DNA应激，并且可以加剧具有DNA损伤反应（DDR）缺陷的细胞中的基因组不稳定性。
Microgravity is a major stress factor that astronauts have to face in space. In the past, the effects of microgravity on genomic DNA damage were studied, and it seems that the effect on genomic DNA depends on cell types and the length of exposure time to microgravity or simulated microgravity (SMG). In this study we used mouse embryonic stem (MES) and mouse embryonic fibroblast (MEF) cells to assess the effects of SMG on DNA lesions. To acquire the insight into potential mechanisms by which cells resist and/or adapt to SMG, we also included Rad9-deleted MES and Mdc1-deleted MEF cells in addition to wild type cells in this study. We observed significant SMG-induced DNA double strand breaks (DSBs) in Rad9 -/- MES and Mdc1 -/- MEF cells but not in their corresponding wild type cells. A similar pattern of DNA single strand break or modifications was also observed in Rad9 -/- MES. As the exposure to SMG was prolonged, Rad9 -/- MES cells adapted to the SMG disturbance by reducing the induced DNA lesions. The induced DNA lesions in Rad9 -/- MES were due to SMG-induced reactive oxygen species (ROS). Interestingly, Mdc1 -/- MEF cells were only partially adapted to the SMG disturbance. That is, the induced DNA lesions were reduced over time, but did not return to the control level while ROS returned to a control level. In addition, ROS was only partially responsible for the induced DNA lesions in Mdc1 -/- MEF cells. Taken together, these data suggest that SMG is a weak genomic DNA stress and can aggravate genomic instability in cells with DNA damage response (DDR) defects.
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影响因子：
11.2
作者：
Hu Z;Liu Y;Zhang C;Zhao Y;He W;Han L;Yang L;Hopkins KM;Yang X;Lieberman HB;Hang H
通讯作者：
Hang H
影响因子：
16
作者：
Lou, ZK;Minter-Dykhouse, K;Chen, JJ
通讯作者：
Chen, JJ
影响因子：
2.7
作者：
Auerbach, W;Dunmore, JH;Joyner, AL
通讯作者：
Joyner, AL
影响因子：
14.9
作者：
Guan, Xin;Bai, Haibo;Lu, A-Lien
通讯作者：
Lu, A-Lien
影响因子：
7.2
作者：
Marechal, Alexandre;Zou, Lee
通讯作者：
Zou, Lee