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dc.contributor.authorLambrus, Bramwell G.
dc.contributor.authorUetake, Yumi
dc.contributor.authorClutario, Kevin M.
dc.contributor.authorDaggubati, Vikas
dc.contributor.authorSnyder, Michael
dc.contributor.authorSluder, Greenfield
dc.contributor.authorHolland, Andrew J.
dc.date2022-08-11T08:08:03.000
dc.date.accessioned2022-08-23T15:40:47Z
dc.date.available2022-08-23T15:40:47Z
dc.date.issued2015-07-06
dc.date.submitted2015-10-13
dc.identifier.citationJ Cell Biol. 2015 Jul 6;210(1):63-77. doi: 10.1083/jcb.201502089. <a href="http://dx.doi.org/10.1083/jcb.201502089">Link to article on publisher's site</a>
dc.identifier.issn0021-9525 (Linking)
dc.identifier.doi10.1083/jcb.201502089
dc.identifier.pmid26150389
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26480
dc.description.abstractCentriole function has been difficult to study because of a lack of specific tools that allow persistent and reversible centriole depletion. Here we combined gene targeting with an auxin-inducible degradation system to achieve rapid, titratable, and reversible control of Polo-like kinase 4 (Plk4), a master regulator of centriole biogenesis. Depletion of Plk4 led to a failure of centriole duplication that produced an irreversible cell cycle arrest within a few divisions. This arrest was not a result of a prolonged mitosis, chromosome segregation errors, or cytokinesis failure. Depleting p53 allowed cells that fail centriole duplication to proliferate indefinitely. Washout of auxin and restoration of endogenous Plk4 levels in cells that lack centrioles led to the penetrant formation of de novo centrioles that gained the ability to organize microtubules and duplicate. In summary, we uncover a p53-dependent surveillance mechanism that protects against genome instability by preventing cell growth after centriole duplication failure.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26150389&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<p>© 2015 Lambrus et al. This article is distributed under the terms of an Attribution– Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).</p>
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/
dc.subjectCell Cycle Checkpoints
dc.subjectCell Line
dc.subjectCell Proliferation
dc.subjectCentrioles
dc.subjectChromosome Segregation
dc.subject*Genomic Instability
dc.subjectHumans
dc.subjectMicrotubules
dc.subjectMitosis
dc.subjectProtein Transport
dc.subjectProtein-Serine-Threonine Kinases
dc.subjectTumor Suppressor Protein p53
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectGenetics
dc.subjectGenomics
dc.titlep53 protects against genome instability following centriole duplication failure
dc.typeJournal Article
dc.source.journaltitleThe Journal of cell biology
dc.source.volume210
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1164&amp;context=cellbiology_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cellbiology_pp/165
dc.identifier.contextkey7709832
refterms.dateFOA2022-08-23T15:40:47Z
html.description.abstract<p>Centriole function has been difficult to study because of a lack of specific tools that allow persistent and reversible centriole depletion. Here we combined gene targeting with an auxin-inducible degradation system to achieve rapid, titratable, and reversible control of Polo-like kinase 4 (Plk4), a master regulator of centriole biogenesis. Depletion of Plk4 led to a failure of centriole duplication that produced an irreversible cell cycle arrest within a few divisions. This arrest was not a result of a prolonged mitosis, chromosome segregation errors, or cytokinesis failure. Depleting p53 allowed cells that fail centriole duplication to proliferate indefinitely. Washout of auxin and restoration of endogenous Plk4 levels in cells that lack centrioles led to the penetrant formation of de novo centrioles that gained the ability to organize microtubules and duplicate. In summary, we uncover a p53-dependent surveillance mechanism that protects against genome instability by preventing cell growth after centriole duplication failure.</p>
dc.identifier.submissionpathcellbiology_pp/165
dc.contributor.departmentDepartment of Cell and Developmental Biology
dc.source.pages63-77


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<p>© 2015 Lambrus et al. This article is distributed under the terms of an Attribution– Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).</p>
Except where otherwise noted, this item's license is described as <p>© 2015 Lambrus et al. This article is distributed under the terms of an Attribution– Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).</p>