Title |
Fluctuations in p53 Signaling Allow Escape from Cell-Cycle Arrest
|
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Published in |
Molecular Cell, July 2018
|
DOI | 10.1016/j.molcel.2018.06.031 |
Pubmed ID | |
Authors |
José Reyes, Jia-Yun Chen, Jacob Stewart-Ornstein, Kyle W. Karhohs, Caroline S. Mock, Galit Lahav |
Abstract |
Biological signals need to be robust and filter small fluctuations yet maintain sensitivity to signals across a wide range of magnitudes. Here, we studied how fluctuations in DNA damage signaling relate to maintenance of long-term cell-cycle arrest. Using live-cell imaging, we quantified division profiles of individual human cells in the course of 1 week after irradiation. We found a subset of cells that initially establish cell-cycle arrest and then sporadically escape and divide. Using fluorescent reporters and mathematical modeling, we determined that fluctuations in the oscillatory pattern of the tumor suppressor p53 trigger a sharp switch between p21 and CDK2, leading to escape from arrest. Transient perturbation of p53 stability mimicked the noise in individual cells and was sufficient to trigger escape from arrest. Our results show that the self-reinforcing circuitry that mediates cell-cycle transitions can translate small fluctuations in p53 signaling into large phenotypic changes. |
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Scientists | 11 | 48% |
Mendeley readers
Geographical breakdown
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Unknown | 234 | 100% |
Demographic breakdown
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Researcher | 36 | 15% |
Student > Bachelor | 29 | 12% |
Student > Master | 20 | 9% |
Student > Doctoral Student | 11 | 5% |
Other | 36 | 15% |
Unknown | 53 | 23% |
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