Autophagy as the effector and player in DNA damage response of cells to genotoxicants
Autophagy as the effector and player in DNA damage response of cells to genotoxicants
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自噬作为细胞对遗传毒物的 DNA 损伤反应的效应器和参与者
DOI：
10.1039/c5tx00043b
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发表时间：
2015-04
影响因子：
2.1
通讯作者：
Zhou Pingkun
中科院分区：
文献类型：
--
作者：
Zhang Shimeng;Shang Zengfu;Zhou Pingkun
自噬是真核细胞中一种高度保守的途径，在各种刺激物的诱导下，自噬可以清除多余或受损的细胞器或异常聚集的蛋白质，以维持细胞内环境的稳定。在过去的十年里，我们对自噬的认识取得了显著的进展，不仅在分子机制方面，而且在各种环境胁迫的生物学效应或某些人类疾病的发展中起着重要作用。真核细胞的基因组不断受到内源性和外源性基因毒性因子的威胁。近年来的研究表明，自噬不仅是遗传毒性物质的基本效应之一，而且在遗传毒性应激的DNA损伤反应中起着重要作用。ATM、p53、PARP-1、DNA-PKcs、TIP 60等一系列DNA损伤反应（DDR）蛋白在DNA损伤诱导的自噬中发挥重要作用，是促进细胞存活的一种保护性措施。自噬还参与细胞对DNA损伤的应答，如细胞周期调控、细胞凋亡等。尽管自噬在DDR中的重要性已经被认识到，但仍然有很多问题需要回答。例如，细胞如何将细胞核DDR信号传递到胞质溶胶以启动自噬; DDR相关的自噬决定细胞存活或细胞死亡途径的机制是什么;以及自噬与慢性低剂量毒物暴露的致癌潜力相关的机制是什么？本文综述了DNA损伤诱导自噬的分子机制、自噬与DNA损伤的相互调节及其在环境毒物遗传毒性作用下细胞命运决定中的作用。
Autophagy is a highly conserved pathway in eukaryotic cells induced by a variety of stimuli to remove superfluous or damaged organelles or abnormally aggregated proteins to maintain cellular homeostasis. A remarkable progress in our understanding of autophagy has been made in the past decade, not only regarding the molecular mechanism, but also its fundamental roles in the biological effects of various environmental stresses or the development of some human diseases. The genome of eukaryotic cells is constantly threatened by endogenous and exogenous genotoxic factors. Research in recent years has demonstrated that autophagy is not only one of the fundamental effects of genotoxicants but also a critical player in DNA damage response to genotoxic stress. A series of DNA damage response (DDR) proteins including ATM, p53, PARP-1, DNA-PKcs, TIP60, and so on have been demonstrated to play important roles in DNA damage induced autophagy, which functions as a protective measure to promote cell survival. Autophagy was also shown to play roles in the cellular responses to DNA damage, e.g. cell cycle regulation, apoptosis. Although the importance of autophagy in DDR has been recognized, there are still a lot of questions to answer. For example, how does the cell transduce the nuclei DDR signal to the cytosol to initiate autophagy; what is the mechanism of DDR related autophagy determining cell survival or cell death pathway; and what is the mechanism associating the autophagy and carcinogenesis potential of chronic low dose exposure of toxicants? In this review, we provide an overview and discuss the molecular mechanism of DNA damage induced autophagy, and their mutual regulation and its role in cell fate determination in response to genotoxic effects of environmental toxicants.
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影响因子：
2.1
作者：
Li, Yufeng;Li, Qinnuan;Zhang, Xiaoyong;Li, Wenxin
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DOI：
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发表时间：
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期刊：
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影响因子：
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影响因子：
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影响因子：
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作者：
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DOI：
10.1042/bj20111451
发表时间：
2012-01-15
期刊：
The Biochemical journal
影响因子：
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