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| Item Type: | Article |
|---|---|
| Title: | PCNA-mediated degradation of p21 coordinates the DNA damage response and cell cycle regulation in individual cells |
| Creators Name: | Sheng, C. and Mendler, I.H. and Rieke, S. and Snyder, P. and Jentsch, M. and Friedrich, D. and Drossel, B. and Loewer, A. |
| Abstract: | 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-CRL4(cdt2) 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. |
| Keywords: | p53 Signaling, Cell Cycle Regulation, Single-Cell Analysis, Cellular Heterogeneity, Mathematical Modeling, Shape-Based Clustering, p21, PCNA, Genome Engineering, Time-Lapse Microscopy |
| Source: | Cell Reports |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 27 |
| Number: | 1 |
| Page Range: | 48-58 |
| Date: | 2 April 2019 |
| Official Publication: | https://doi.org/10.1016/j.celrep.2019.03.031 |
| PubMed: | View item in PubMed |
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