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The Aurora-B-dependent NoCut checkpoint prevents damage of anaphase bridges after DNA replication stress

AuthorsAmaral, Nuno; Idrissi, Fátima-Zahra ; Mendoza, Manuel
KeywordsCell division, checkpoints, cytokeneis, DNA damage and repair
Issue Date25-Apr-2016
PublisherNature Publishing Group
CitationNature Cell Biology 18: 516-526 (2016)
AbstractAnaphase chromatin bridges can lead to chromosome breakage if not properly resolved before completion of cytokinesis. The NoCut checkpoint, which depends on Aurora B at the spindle midzone, delays abscission in response to chromosome segregation defects in yeast and animal cells. How chromatin bridges are detected, and whether abscission inhibition prevents their damage, remain key unresolved questions. We find that bridges induced by DNA replication stress and by condensation or decatenation defects, but not dicentric chromosomes, delay abscission in a NoCut-dependent manner. Decatenation and condensation defects lead to spindle stabilization during cytokinesis, allowing bridge detection by Aurora B. NoCut does not prevent DNA damage following condensin or topoisomerase II inactivation; however, it protects anaphase bridges and promotes cellular viability after replication stress. Therefore, the molecular origin of chromatin bridges is critical for activation of NoCut, which plays a key role in the maintenance of genome stability after replicative stress.
DescriptionNuno Amaral et al.
Publisher version (URL)http://dx.doi.org/10.1038/ncb3343
Identifiersdoi: 10.1038/ncb3343
issn: 1476-4679
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