Sheng, Caibin ; Mendler, Isabella-Hilda ; Rieke, Sara ; Snyder, Petra ; Jentsch, Marc ; Friedrich, Dhana ; Drossel, Barbara ; Loewer, Alexander (2019)
PCNA-Mediated Degradation of p21 Coordinates the DNA Damage Response and Cell Cycle Regulation in Individual Cells.
In: Cell Reports, 27 (1)
doi: 10.1016/j.celrep.2019.03.031
Artikel, Bibliographie
Kurzbeschreibung (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-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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2019 |
| Autor(en): | Sheng, Caibin ; Mendler, Isabella-Hilda ; Rieke, Sara ; Snyder, Petra ; Jentsch, Marc ; Friedrich, Dhana ; Drossel, Barbara ; Loewer, Alexander |
| Art des Eintrags: | Bibliographie |
| Titel: | PCNA-Mediated Degradation of p21 Coordinates the DNA Damage Response and Cell Cycle Regulation in Individual Cells |
| Sprache: | Englisch |
| Publikationsjahr: | 2 April 2019 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Cell Reports |
| Jahrgang/Volume einer Zeitschrift: | 27 |
| (Heft-)Nummer: | 1 |
| DOI: | 10.1016/j.celrep.2019.03.031 |
| URL / URN: | https://doi.org/10.1016/j.celrep.2019.03.031 |
| Kurzbeschreibung (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-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. |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Systems Biology of the Stress Response DFG-Graduiertenkollegs DFG-Graduiertenkollegs > Graduiertenkolleg 1657 Molekulare und zelluläre Reaktionen auf ionisierende Strahlung 05 Fachbereich Physik 05 Fachbereich Physik > Institut für Festkörperphysik (2021 umbenannt in Institut für Physik Kondensierter Materie (IPKM)) 05 Fachbereich Physik > Institut für Festkörperphysik (2021 umbenannt in Institut für Physik Kondensierter Materie (IPKM)) > Statistische Physik und komplexe Systeme |
| Hinterlegungsdatum: | 15 Apr 2019 09:33 |
| Letzte Änderung: | 15 Apr 2019 09:33 |
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