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dc.contributor.authorGeva-Zatorsky, Naama
dc.contributor.authorRosenfeld, Nitzan
dc.contributor.authorItzkovitz, Shalev
dc.contributor.authorSigal, Alex
dc.contributor.authorDekel, Erez
dc.contributor.authorYarnitzky, Talia
dc.contributor.authorLiron, Yuvalal
dc.contributor.authorPolak, Paz
dc.contributor.authorAlon, Uri
dc.contributor.authorMilo, Ron
dc.contributor.authorLahav, Galit
dc.date.accessioned2010-10-25T15:47:30Z
dc.date.issued2006
dc.identifier.citationGeva-Zatorsky, Naama, Nitzan Rosenfeld, Shalev Itzkovitz, Ron Milo, Alex Sigal, Erez Dekel, Talia Yarnitzky, et al. 2006. Oscillations and variability in the p53 system. Molecular Systems Biology 2:2006.0033.en_US
dc.identifier.issn1744-4292en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4506437
dc.description.abstractUnderstanding the dynamics and variability of protein circuitry requires accurate measurements in living cells as well as theoretical models. To address this, we employed one of the best-studied protein circuits in human cells, the negative feedback loop between the tumor suppressor p53 and the oncogene Mdm2. We measured the dynamics of fluorescently tagged p53 and Mdm2 over several days in individual living cells. We found that isogenic cells in the same environment behaved in highly variable ways following DNA-damaging gamma irradiation: some cells showed undamped oscillations for at least 3 days (more than 10 peaks). The amplitude of the oscillations was much more variable than the period. Sister cells continued to oscillate in a correlated way after cell division, but lost correlation after about 11 h on average. Other cells showed low-frequency fluctuations that did not resemble oscillations. We also analyzed different families of mathematical models of the system, including a novel checkpoint mechanism. The models point to the possible source of the variability in the oscillations: low-frequency noise in protein production rates, rather than noise in other parameters such as degradation rates. This study provides a view of the extensive variability of the behavior of a protein circuit in living human cells, both from cell to cell and in the same cell over time.en_US
dc.description.sponsorshipMolecular and Cellular Biologyen_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofdoi:10.1038/msb4100068en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1681500/pdf/en_US
dash.licenseLAA
dc.subjectcancer geneticsen_US
dc.subjectfluorescence microscopyen_US
dc.subjectquantitative biologyen_US
dc.subjectsystems biologyen_US
dc.titleOscillations and Variability in the P53 Systemen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalMolecular Systems Biologyen_US
dash.depositing.authorLahav, Galit
dc.date.available2010-10-25T15:47:30Z
dc.identifier.doi10.1038/msb4100068*
dash.authorsorderedfalse
dash.contributor.affiliatedLahav, Galit
dash.contributor.affiliatedMilo, Ron


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