Long-term p21 and p53 dynamics regulate the frequency of mitosis events and cell cycle arrest following radiation damage

被引:0
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作者
Anh Phong Tran
Christopher J. Tralie
José Reyes
Caroline Moosmüller
Zehor Belkhatir
Ioannis G. Kevrekidis
Arnold J. Levine
Joseph O. Deasy
Allen R. Tannenbaum
机构
[1] Memorial Sloan Kettering Cancer Center,Department of Medical Physics
[2] Ursinus College,Department of Mathematics and Computer Science
[3] Memorial Sloan Kettering Cancer Center,Cancer Biology and Genetics Program and Computational and Systems Biology Program
[4] Harvard Medical School,Department of Systems Biology
[5] University of California,Department of Mathematics
[6] San Diego,School of Engineering and Sustainable Development
[7] De Montfort University,Department of Chemical and Biological Engineering
[8] Johns Hopkins University,Simons Center for Systems Biology
[9] Institute for Advanced Study,Departments of Computer Science and Applied Mathematics & Statistics
[10] Stony Brook University,undefined
来源
Cell Death & Differentiation | 2023年 / 30卷
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摘要
Radiation exposure of healthy cells can halt cell cycle temporarily or permanently. In this work, we analyze the time evolution of p21 and p53 from two single cell datasets of retinal pigment epithelial cells exposed to several levels of radiation, and in particular, the effect of radiation on cell cycle arrest. Employing various quantification methods from signal processing, we show how p21 levels, and to a lesser extent p53 levels, dictate whether the cells are arrested in their cell cycle and how frequently these mitosis events are likely to occur. We observed that single cells exposed to the same dose of DNA damage exhibit heterogeneity in cellular outcomes and that the frequency of cell division is a more accurate monitor of cell damage rather than just radiation level. Finally, we show how heterogeneity in DNA damage signaling is manifested early in the response to radiation exposure level and has potential to predict long-term fate.
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页码:660 / 672
页数:12
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