dc.contributor.author
Gutu, Nica
dc.contributor.author
Binish, Neha
dc.contributor.author
Keilholz, Ulrich
dc.contributor.author
Herzel, Hanspeter
dc.contributor.author
Granada, Adrián E.
dc.date.accessioned
2025-09-17T11:14:22Z
dc.date.available
2025-09-17T11:14:22Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/49374
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-49096
dc.description.abstract
Cells must accurately and quickly detect DNA damage through a set of checkpoint mechanisms that enable repair and control proliferation. Heterogeneous levels of cellular stress and noisy signaling processes can lead to phenotypic variability but little is known about their role in underlying proliferation heterogeneity. Here we study two previously published single cell datasets and find that cells encode heterogeneous levels of endogenous and exogenous DNA damage to shape proliferation heterogeneity at the population level. Using a comprehensive time series analysis of short- and long-term signaling dynamics of p53 and p21, we show that DNA damage levels are quantitatively translated into p53 and p21 signal parameters in a gradual manner. Analyzing instantaneous proliferation and signaling differences among equally-radiated cells, we identify time-localized changes in the period of p53 pulses that drive cells out of a low proliferative state. Our findings suggest a novel role of the p53-p21 network in quantitatively encoding DNA damage strength and fine-tuning proliferation trajectories.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Cell Proliferation
en
dc.subject
Cyclin-Dependent Kinase Inhibitor p21 / genetics
en
dc.subject
Signal Transduction
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
p53 and p21 dynamics encode single-cell DNA damage levels, fine-tuning proliferation and shaping population heterogeneity
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
1196
dcterms.bibliographicCitation.doi
10.1038/s42003-023-05585-5
dcterms.bibliographicCitation.journaltitle
Communications Biology
dcterms.bibliographicCitation.number
1
dcterms.bibliographicCitation.originalpublishername
Springer Nature
dcterms.bibliographicCitation.volume
6
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
Springer Nature DEAL
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
38001355
dcterms.isPartOf.eissn
2399-3642