| Autor: |
Caibin Sheng, Isabella-Hilda Mendler, Sara Rieke, Petra Snyder, Marcel Jentsch, Dhana Friedrich, Barbara Drossel, Alexander Loewer |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 27, Iss 1, Pp 48-58.e7 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.03.031 |
| Popis: |
Summary: To enable reliable cell fate decisions, mammalian cells need to adjust their responses to dynamically changing internal states by rewiring the corresponding signaling networks. Here, we combine time-lapse microscopy of endogenous fluorescent reporters with computational analysis to understand at the single-cell level how the p53-mediated DNA damage response is adjusted during cell cycle progression. Shape-based clustering revealed that the dynamics of the CDK inhibitor p21 diverges from the dynamics of its transcription factor p53 during S phase. Using mathematical modeling, we predict and experimentally validate that S phase-specific degradation of p21 by PCNA-CRL4cdt2 is sufficient to explain these heterogeneous responses. This highlights how signaling pathways and cell regulatory networks intertwine to adjust the cellular response to the individual needs of a given cell. : Combining live-cell microscopy of endogenous fluorescent reporters with computational analysis, Sheng et al. investigate how the p53-mediated response to ionizing radiation is adjusted to cellular states. They demonstrate that heterogeneous p21 dynamics post damage are caused by S phase-specific degradation through PCNA-CRL4cdt2, which is necessary for maintaining genome stability. Keywords: p53 signaling, cell cycle regulation, single-cell analysis, cellular heterogeneity, mathematical modeling, shape-based clustering, p21, PCNA, genome engineering, time-lapse microscopy |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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