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

Autor: Fatima-Zahra Idrissi, Jordi Torres-Rosell, Arun Kumar, Neus Colomina, Manuel Mendoza, Gabriel Neurohr, Charlotta Funaya, Alexandre Vendrell, María-Isabel Geli, Nuno Amaral, Michael Maier
Přispěvatelé: Ministerio de Economía y Competitividad (España), La Caixa, Electron Microscopy Core Facility, Universität Heidelberg [Heidelberg], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2016
Předmět:
Zdroj: Recercat. Dipósit de la Recerca de Catalunya
instname
Nature Cell Biology
Nature Cell Biology, Nature Publishing Group, 2016, 18 (5), pp.516-526. ⟨10.1038/ncb3343⟩
Digital.CSIC. Repositorio Institucional del CSIC
ISSN: 1476-4679
1465-7392
DOI: 10.1038/ncb3343
Popis: Nuno Amaral et al.
Anaphase 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.
This research was supported by ‘La Caixa’ fellowships to N.A., G.N. and M.Maier, and grants from the Spanish Ministry of Economy and Competitivity (BFU2011-30185 and CDS2009-00016 to M.-I.G.; BFU2015-71308 and BFU2013-50245-EXP to J.T.-R.; and BFU2009-08213 and BFU2012-37162 to M.Mendoza), and from the European Research Council (ERC Starting Grant 260965 to M.Mendoza). We acknowledge support from the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208
Databáze: OpenAIRE