The role of autophagy in genome stability through suppression of abnormal mitosis under starvation
| العنوان: | The role of autophagy in genome stability through suppression of abnormal mitosis under starvation |
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| المؤلفون: | Aiko Matsui, Akira Matsuura, Yoshiaki Kamada |
| المصدر: | PLoS Genetics, Vol 9, Iss 1, p e1003245 (2013) PLoS Genetics |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | G2 Phase, Cancer Research, Saccharomyces cerevisiae Proteins, Cell division, lcsh:QH426-470, Nitrogen, Saccharomyces cerevisiae, Cell, Mitosis, Yeast and Fungal Models, Genomic Instability, Cell Growth, Molecular Genetics, Model Organisms, Genetic Mutation, Molecular Cell Biology, Autophagy, Genetics, medicine, Amino Acids, Biology, Molecular Biology, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Cell Proliferation, Cellular Stress Responses, Starvation, biology, Chromosome Biology, Cell growth, G1 Phase, Cell cycle, Aneuploidy, biology.organism_classification, Cell biology, G2 Phase Cell Cycle Checkpoints, lcsh:Genetics, medicine.anatomical_structure, Biochemistry, Gene Function, medicine.symptom, Cell Division, Transcription Factors, Research Article |
| الوصف: | 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. Author Summary 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. |
| اللغة: | English |
| تدمد: | 1553-7404 1553-7390 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::98574e48301d4757cf864df17db60e4dTest http://europepmc.org/articles/PMC3561091?pdf=renderTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....98574e48301d4757cf864df17db60e4d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537404 15537390 |
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