Long-term p21 and p53 dynamics regulate the frequency of mitosis events and cell cycle arrest following radiation damage Journal Article
| Authors: | Tran, A. P.; Tralie, C. J.; Reyes, J.; Moosmüller, C.; Belkhatir, Z.; Kevrekidis, I. G.; Levine, A. J.; Deasy, J. O.; Tannenbaum, A. R. |
| Article Title: | Long-term p21 and p53 dynamics regulate the frequency of mitosis events and cell cycle arrest following radiation damage |
| Abstract: | 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. © 2022, The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare. |
| Keywords: | controlled study; human cell; mitosis; protein analysis; metabolism; dna damage; cell cycle; molecular dynamics; radiation injury; protein p53; radiation exposure; radiation response; cell heterogeneity; dna; tumor suppressor protein p53; cell cycle arrest; cell cycle checkpoint; mitosis rate; cyclin dependent kinase inhibitor 1a; cyclin-dependent kinase inhibitor p21; protein p21; signal processing; single cell analysis; cell cycle checkpoints; human; article; retina pigment cell |
| Journal Title: | Cell Death and Differentiation |
| Volume: | 30 |
| Issue: | 3 |
| ISSN: | 1350-9047 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-03-01 |
| Start Page: | 660 |
| End Page: | 672 |
| Language: | English |
| DOI: | 10.1038/s41418-022-01069-x |
| PUBMED: | 36182991 |
| PROVIDER: | scopus |
| PMCID: | PMC9984379 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
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