Analysis of cell cycle parameters during the transition from unhindered growth to ribosomal and translational stress conditions

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dc.contributorPolymenis, Michael
dc.contributor.authorShamsuzzaman, Md
dc.contributor.authorBommakanti, Ananth
dc.contributor.authorZapinsky, Aviva
dc.contributor.authorRahman, Nusrat
dc.contributor.authorPascual, Clarence
dc.contributor.authorLindahl, Lasse
dc.date.accessioned2019-06-20T19:25:19Z
dc.date.available2019-06-20T19:25:19Z
dc.date.issued2017-10-13
dc.description.abstractAbrogation of ribosome synthesis (ribosomal stress) leads to cell cycle arrest. However, the immediate cell response to cessation of ribosome formation and the transition from normal cell proliferation to cell cycle arrest have not been characterized. Furthermore, there are conflicting conclusions about whether cells are arrested in G2/M or G1, and whether the cause is dismantling ribosomal assembly per se, or the ensuing decreased number of translating ribosomes. To address these questions, we have compared the time kinetics of key cell cycle parameters after inhibiting ribosome formation or function in Saccharomyces cerevisiae. Within one-to-two hours of repressing genes for individual ribosomal proteins or Translation Elongation factor 3, configurations of spindles, spindle pole bodies began changing. Actin began depolarizing within 4 hours. Thus the loss of ribosome formation and function is sensed immediately. After several hours no spindles or mitotic actin rings were visible, but membrane ingression was completed in most cells and Ace2 was localized to daughter cell nuclei demonstrating that the G1 stage was reached. Thus cell division was completed without the help of a contractile actin ring. Moreover, cell wall material held mother and daughter cells together resulting in delayed cell separation, suggesting that expression or function of daughter gluconases and chitinases is inhibited. Moreover, cell development changes in very similar ways in response to inhibition of ribosome formation and function, compatible with the notion that decreased translation capacity contributes to arresting the cell cycle after abrogation of ribosome biogenesis. Potential implications for the mechanisms of diseases caused by mutations in ribosomal genes (ribosomopathies) are discussed.en_US
dc.description.sponsorshipThis study was supported by the National Science Foundation, https://www.nsf.gov/, MCB0920578; the National Science Foundation, https://www.nsf.gov/, DBI-0722569; and the Provost's Office, University of Maryland Baltimore County to LL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.description.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186494en_US
dc.format.extent25 pagesen_US
dc.genrejournal articlesen_US
dc.identifierdoi:10.13016/m2wvof-b53j
dc.identifier.citationShamsuzzaman M, Bommakanti A, Zapinsky A, Rahman N, Pascual C, Lindahl L (2017) Analysis of cell cycle parameters during the transition from unhindered growth to ribosomal and translational stress conditions. PLoS ONE 12 (10): e0186494. https://doi.org/10.1371/journal. pone.0186494en_US
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0186494
dc.identifier.urihttp://hdl.handle.net/11603/14282
dc.language.isoen_USen_US
dc.publisherPLOSen_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Biological Sciences Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectribosomalen_US
dc.subjecttranslational stress conditionsen_US
dc.subjectSaccharomyces cerevisiaeen_US
dc.subjectcell cycle parametersen_US
dc.titleAnalysis of cell cycle parameters during the transition from unhindered growth to ribosomal and translational stress conditionsen_US
dc.typeTexten_US

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