The NoCut pathway links completion of cytokinesis to spindle midzone function to prevent chromosome breakage.
During anaphase, spindle elongation pulls sister chromatids apart until each pair is fully separated. In turn, cytokinesis cleaves the cell between the separated chromosomes. What ensures that cytokinesis proceeds only after that all chromosome arms are pulled out of the cleavage plane was unknown. Here, we show that a signaling pathway, which we call NoCut, delays the completion of cytokinesis in cells with spindle-midzone defects. NoCut depends on the Aurora kinase Ipl1 and the anillin-related proteins Boi1 and Boi2, which localize to the site of cleavage in an Ipl1-dependent manner and act as abscission inhibitors. Inactivation of NoCut leads to premature abscission and chromosome breakage by the cytokinetic machinery and is lethal in cells with spindle-elongation defects. We propose that NoCut monitors clearance of chromatin from the midzone to ensure that cytokinesis completes only after all chromosomes have migrated to the poles.
Norden
Caren
C
Institute of Biochemistry, Biology Department, ETH Zurich, 8093 Zurich, Switzerland.
Mendoza
Manuel
M
Dobbelaere
Jeroen
J
Kotwaliwale
Chitra V
CV
Biggins
Sue
S
Barral
Yves
Y
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D064127:Aurora Kinases; D019457:Chromosome Breakage; D015825:Chromosomes, Fungal / Q000502:physiology*; D048749:Cytokinesis / Q000502:physiology*; D018386:Kinetochores / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C472767:Ase1 protein, S cerevisiae; C099888:BOI1 protein, S cerevisiae; C099887:BOI2 protein, S cerevisiae; D008869:Microtubule-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases