Slow-growing cells within isogenic populations have increased RNA polymerase error rates and DNA damage
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- dc.contributor.author Dijk, David vanca
- dc.contributor.author Dhar, Riddhimanca
- dc.contributor.author Missarova, Alsu, 1990-ca
- dc.contributor.author Espinar, Lorenaca
- dc.contributor.author Blevins, William Robert, 1987-ca
- dc.contributor.author Lehner, Ben, 1978-ca
- dc.contributor.author Carey, Lucas, 1980-ca
- dc.date.accessioned 2015-11-17T14:00:17Z
- dc.date.available 2015-11-17T14:00:17Z
- dc.date.issued 2015
- dc.description.abstract Isogenic cells show a large degree of variability in growth rate, even when cultured in the same environment. Such cell-to-cell variability in growth can alter sensitivity to antibiotics, chemotherapy and environmental stress. To characterize transcriptional differences associated with this variability, we have developed a method--FitFlow--that enables the sorting of subpopulations by growth rate. The slow-growing subpopulation shows a transcriptional stress response, but, more surprisingly, these cells have reduced RNA polymerase fidelity and exhibit a DNA damage response. As DNA damage is often caused by oxidative stress, we test the addition of an antioxidant, and find that it reduces the size of the slow-growing population. More generally, we find a significantly altered transcriptome in the slow-growing subpopulation that only partially resembles that of cells growing slowly due to environmental and culture conditions. Slow-growing cells upregulate transposons and express more chromosomal, viral and plasmid-borne transcripts, and thus explore a larger genotypic--and so phenotypic--space.en
- dc.description.sponsorship This work was supported by grants to B.L. from the European Research Council Consolidator Grant (IR-DC 616434), Spanish Ministry of Economy and Competitiveness (BFU2011-26206), the AXA Research Fund, Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR), and the EMBL-CRG Systems Biology Program. This work was supported by grants to L.B.C. from the department and the AGAUR program (2014 SGR 0974). R.D. acknowledges support from Swiss National Science Foundation through Early Postdoc Mobility Fellowship. D.v.D. was supported by an NWO Rubicon fellowship (825.14.016).en
- dc.format.mimetype application/pdfca
- dc.identifier.citation van Dijk D, Dhar R, Missarova AM, Espinar L, Blevins WR, Lehner B et al. Slow-growing cells within isogenic populations have increased RNA polymerase error rates and DNA damage. Nature communications. 2015;6:7972. DOI: 10.1038/ncomms8972ca
- dc.identifier.doi http://dx.doi.org/10.1038/ncomms8972
- dc.identifier.issn 2041-1723
- dc.identifier.uri http://hdl.handle.net/10230/25114
- dc.language.iso engca
- dc.publisher Nature Publishing Groupca
- dc.relation.ispartof Nature communications. 2015;6:7972
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/616434
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-26206
- dc.rights © 2015 Macmillan Publishers Limited. All rights reserved. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.en
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
- dc.subject.other Transcripció genètica
- dc.subject.other ADN -- Dany
- dc.title Slow-growing cells within isogenic populations have increased RNA polymerase error rates and DNA damageen
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca