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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The availability of the code to reproduce the results as well as the algorithms made in this work are made available at https://github.com/phongatran/p21p53/.
The data that support the findings of this study are available upon request through the corresponding author.
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The authors thank Professor Galit Lahav from Havard Medical School for making the data available to use in this study as well as the support of Memorial Sloan Kettering Cancer Center that made this work possible.
This study was supported by AFOSR grant (FA9550-17-1-0435), a grant from National Institutes of Health (R01-AG048769), MSK Cancer Center Support Grant/Core Grant (P30 CA008748), and a grant from Breast Cancer Research Foundation (BCRF-17-193). C.M. is supported by NSF DMS grant 2111322. J.R. received support from CONACyT/Fundacion Mexico en Harvard (404476), and Harvard Graduate Merit Fellowship.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Tran, A.P., Tralie, C.J., Reyes, J. et al. Long-term p21 and p53 dynamics regulate the frequency of mitosis events and cell cycle arrest following radiation damage. Cell Death Differ (2022). https://doi.org/10.1038/s41418-022-01069-x