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dc.contributor.authorVarmark, Hanne
dc.contributor.authorSparks, Cynthia A.
dc.contributor.authorNordberg, Joshua J.
dc.contributor.authorKoppetsch, Birgit S.
dc.contributor.authorTheurkauf, William E.
dc.date2022-08-11T08:09:39.000
dc.date.accessioned2022-08-23T16:38:44Z
dc.date.available2022-08-23T16:38:44Z
dc.date.issued2009-08-29
dc.date.submitted2010-03-29
dc.identifier.citation<p>Cell Cycle. 2009 Sep 15;8(18):2951-63. Epub 2009 Sep 16.</p>
dc.identifier.issn1551-4005 (Linking)
dc.identifier.pmid19713770
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39312
dc.description.abstractProgression through the G(2)/M transition following DNA damage is linked to cytokinesis failure and mitotic death. In four different transformed cell lines and two human embryonic stem cell lines, we find that DNA damage triggers mitotic chromatin decondensation and global phosphorylation of histone H2AX, which has been associated with apoptosis. However, extended time-lapse studies in HCT116 colorectal cancer cells indicate that death does not take place during mitosis, but 72% of cells die within 3 days of mitotic exit. By contrast, only 11% of cells in the same cultures that remained in interphase died, suggesting that progression through mitosis enhances cell death following DNA damage. These time-lapse studies also confirmed that DNA damage leads to high rates of cytokinesis failure, but showed that cells that completed cytokinesis following damage died at higher rates than cells that failed to complete division. Therefore, post-mitotic cell death is not a response to cytokinesis failure or polyploidy. We also show that post-mitotic cell death is largely independent of p53 and is only partially suppressed by the apical caspase inhibitor Z-VAD-FMK. These findings suggest that progression through mitosis following DNA damage initiates a p53- and caspase-independent cell death response that prevents propagation of genetic lesions.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=19713770&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897049/
dc.subjectCaspases
dc.subjectCell Death
dc.subjectCell Line
dc.subjectCell Line, Tumor
dc.subjectCytokinesis
dc.subject*DNA Damage
dc.subjectEmbryonic Stem Cells
dc.subjectHCT116 Cells
dc.subjectHumans
dc.subjectKinetics
dc.subject*Mitosis
dc.subjectTumor Suppressor Protein p53
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleDNA damage-induced cell death is enhanced by progression through mitosis
dc.typeJournal Article
dc.source.journaltitleCell cycle (Georgetown, Tex.)
dc.source.volume8
dc.source.issue18
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2112
dc.identifier.contextkey1250242
html.description.abstract<p>Progression through the G(2)/M transition following DNA damage is linked to cytokinesis failure and mitotic death. In four different transformed cell lines and two human embryonic stem cell lines, we find that DNA damage triggers mitotic chromatin decondensation and global phosphorylation of histone H2AX, which has been associated with apoptosis. However, extended time-lapse studies in HCT116 colorectal cancer cells indicate that death does not take place during mitosis, but 72% of cells die within 3 days of mitotic exit. By contrast, only 11% of cells in the same cultures that remained in interphase died, suggesting that progression through mitosis enhances cell death following DNA damage. These time-lapse studies also confirmed that DNA damage leads to high rates of cytokinesis failure, but showed that cells that completed cytokinesis following damage died at higher rates than cells that failed to complete division. Therefore, post-mitotic cell death is not a response to cytokinesis failure or polyploidy. We also show that post-mitotic cell death is largely independent of p53 and is only partially suppressed by the apical caspase inhibitor Z-VAD-FMK. These findings suggest that progression through mitosis following DNA damage initiates a p53- and caspase-independent cell death response that prevents propagation of genetic lesions.</p>
dc.identifier.submissionpathoapubs/2112
dc.contributor.departmentDepartment of Cell Biology
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages2951-63


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