The Aurora-B-dependent NoCut checkpoint prevents damage of anaphase bridges after DNA replication stress.
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.
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
Nuno
0000-0003-2501-1403
N
Amaral
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
Alexandre
A
Vendrell
EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany.
Charlotta
C
Funaya
Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, 08028 Barcelona, Spain.
Fatima-Zahra
FZ
Idrissi
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
Michael
M
Maier
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
Arun
A
Kumar
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.
Gabriel
G
Neurohr
Institut de Recerca Biomèdica de Lleida, Av. Alcalde Rovira Roure, 80 25198 Lleida, Spain.
Neus
N
Colomina
Institut de Recerca Biomèdica de Lleida, Av. Alcalde Rovira Roure, 80 25198 Lleida, Spain.
Jordi
J
Torres-Rosell
EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany.
María-Isabel
MI
Geli
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
Manuel
M
Mendoza
D000205:Actomyosin / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000705:Anaphase / Q000187:drug effects; D064127:Aurora Kinases / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000378:metabolism; D006918:Hydroxyurea / Q000494:pharmacology; D050296:Microbial Viability / Q000187:drug effects; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects
C403402:AHC1 protein, S cerevisiae; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C108312:condensin complexes; D000205:Actomyosin; D051548:Histone Acetyltransferases; D064127:Aurora Kinases; C576961:IPL1 protein, S cerevisiae; D000251:Adenosine Triphosphatases; D004250:DNA Topoisomerases, Type II; D006918:Hydroxyurea