Radiation-induced cellular senescence results from a slippage of long-term G2 arrested cells into G1 phase
Radiation-induced cellular senescence results from a slippage of long-term G2 arrested cells into G1 phase
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DOI：
10.4161/cc.24528
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发表时间：
2013-05-01
期刊：
影响因子：
4.3
通讯作者：
Zhou, Guangming
中科院分区：
文献类型：
--
作者：
Ye, Caiyong;Zhang, Xurui;Zhou, Guangming
二倍体细胞经历衰老和有丝分裂滑移已经在文献中报道。然而，触发长期G(2)阻滞细胞衰老的机制目前尚不清楚。先前，我们报道了人类葡萄膜黑色素瘤细胞系92-1在暴露于10gy电离辐射（IR）后，细胞周期暂停长达6天，随后衰老。在目前的研究中，我们通过确认细胞在G(2)期的阻滞，初步区分了长期阻断的92-1细胞的衰老和有丝分裂滑移。我们随后发现，G(2)-M转化所必需的基因在转录和翻译水平上都过早下调。此外，G(1)特异性标志物Cyclin D1和Caveolin-1水平明显升高，而S/G(2)特异性标志物Cyclin B1和Aurora A水平显著下调。这些发现共同表明，长期的G(2)阻滞细胞通过G(2)滑移进行衰老。据我们所知，这是第一个报道G(2)滑移的细胞过程是长期G(2)阻滞下细胞衰老的机制的研究。
Diploid cells undergoing senescence and mitotic slippage have been reported in the literature. However, the mechanisms triggering senescence in long-term G(2)-arrested cells are currently unclear. Previously, we reported that the cell cycle of the human uveal melanoma cell line, 92-1, is suspended for up to 6 d upon exposure to 10 Gy ionizing radiation (IR), followed by senescence. In the current study, we initially distinguished senescence in long-term blocked 92-1 cells from mitotic slippage by confirming the blockage of cells in the G(2) phase. We subsequently showed that the genes essential for G(2)-M transition are prematurely downregulated at both the transcriptional and translational levels. Furthermore, levels of the G(1)-specific markers, Cyclin D1 and Caveolin-1, were distinctly increased, while S/G(2)-specific markers, Cyclin B1 and Aurora A, were significantly downregulated. These findings collectively imply that long-term G(2)-arrested cells undergo senescence via G(2) slippage. To our knowledge, this is the first study to report that the cellular process of G(2) slippage is the mechanism responsible for senescence of cells under long-term G(2) arrest.