The role of autophagy in genome stability through suppression of abnormal mitosis under starvation.
The role of autophagy in genome stability through suppression of abnormal mitosis under starvation.
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DOI：
10.1371/journal.pgen.1003245
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Matsuura A
中科院分区：
文献类型：
--
作者：
Matsui A;Kamada Y;Matsuura A
适应环境变化期间亚细胞过程的协调是生物系统的关键特征。必需营养物质的饥饿会减慢细胞循环并最终导致G1停滞，氮饥饿延迟了G2/m的进展。在这里，我们表明可以在饥饿条件下以自噬依赖性方式有效地返回酵母菌细胞。饥饿减轻了TORC1活性，导致依赖SWE1依赖性检查点机制的G2/M延迟，而饥饿诱导的自噬可以通过提供细胞生长所需的氨基酸来有助于从G2/M延迟中恢复。通过自噬的缺乏，细胞周期的持续延迟会导致异常的核分裂，而没有足够的细胞生长，从而导致氮源后，导致非整倍性频率增加。我们的数据在抑制细胞生长的条件下通过调节细胞分裂来确定自噬在基因组稳定性中的作用。
诸如氮耗竭之类的营养应激会诱导真核细胞中的多效应反应。例如，营养饥饿会减慢细胞循环，并最终导致G1停滞。另外，众所周知，氮饥饿会延迟G2/m的进展。但是，关于G2/M延迟细胞如何通过细胞周期返回G1相的机制尚不清楚。受到养分应激的细胞会诱导自噬，这是溶酶体/液泡内的散装降解系统，以重建细胞成分。在这项研究中，我们表明，氨基酸池的自噬依赖性供应对于在发芽的酵母菌酿酒酵母中的饥饿条件下完成细胞周期至关重要。自噬缺陷会导致细胞生长的缺陷，并导致与较高的非整倍性发生率相关的有丝分裂异常。因此，我们的数据通过在抑制细胞生长的条件下调节细胞分裂来确定自噬在基因组稳定性中的作用，从而提供了通过哺乳动物细胞中显示的自噬抑制肿瘤的机制。
The coordination of subcellular processes during adaptation to environmental change is a key feature of biological systems. Starvation of essential nutrients slows cell cycling and ultimately causes G1 arrest, and nitrogen starvation delays G2/M progression. Here, we show that budding yeast cells can be efficiently returned to the G1 phase under starvation conditions in an autophagy-dependent manner. Starvation attenuates TORC1 activity, causing a G2/M delay in a Swe1-dependent checkpoint mechanism, and starvation-induced autophagy assists in the recovery from a G2/M delay by supplying amino acids required for cell growth. Persistent delay of the cell cycle by a deficiency in autophagy causes aberrant nuclear division without sufficient cell growth, leading to an increased frequency in aneuploidy after refeeding the nitrogen source. Our data establish the role of autophagy in genome stability through modulation of cell division under conditions that repress cell growth. A nutrient stress such as nitrogen depletion induces pleiotropic responses in eukaryotic cells. For example, nutrient starvation slows cell cycling and ultimately causes G1 arrest. In addition, it is known that nitrogen starvation delays G2/M progression. However, the mechanism as to how G2/M-delayed cells progress through the cell cycle to return to the G1 phase remains unclear. Cells subjected to a nutrient stress induce autophagy, a bulk degradation system within lysosomes/vacuoles, to reconstitute cellular components. In this study, we show that an autophagy-dependent supply of amino acid pools is critical for completion of cell cycle under starvation conditions in the budding yeast Saccharomyces cerevisiae. Autophagy deficiency causes a defect in cell growth and leads to abnormal mitosis associated with a higher incidence of aneuploidy. Thus, our data establish the role of autophagy in genome stability through modulation of cell division under conditions that repress cell growth, which provides a possible mechanism of tumor suppression by autophagy shown in mammalian cells.
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影响因子：
16
作者：
Loewith, R;Jacinto, E;Hall, MN
通讯作者：
Hall, MN
DOI：
10.1083/jcb.200412022
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
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作者：
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影响因子：
3.7
作者：
JOHNSTON, GC;PRINGLE, JR;HARTWELL, LH
通讯作者：
HARTWELL, LH