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Nat Cell Biol. 2016 May;18(5):516-26. doi: 10.1038/ncb3343. Epub 2016 Apr 25.

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

Author information

1
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.
2
Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
3
EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany.
4
Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, 08028 Barcelona, Spain.
5
Institut de Recerca Biomèdica de Lleida, Av. Alcalde Rovira Roure, 80 25198 Lleida, Spain.

Abstract

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.

PMID:
27111841
DOI:
10.1038/ncb3343
[Indexed for MEDLINE]

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