2 research outputs found
A midzone-based ruler adjusts chromosome compaction to analphase spindle length
Partitioning of chromatids during mitosis requires that chromosome
compaction and spindle length scale appropriately with each other. However,
it is not clear whether chromosome condensation and spindle elongation are
linked. Here we have used chromosome fusions to examine the impact of
increased chromosome length during yeast mitosis. We find that yeast cells
could cope with a >50% increase in the length of their longest chromosome
arm by decreasing the physical length of the mitotic chromosome arm through
1) reducing the number of copies of the repetitive rDNA array and 2) by
increasing the level of mitotic condensation. Consistently, cells carrying the
fused chromosomes became more sensitive to loss of condensin- and its
regulator polo kinase/Cdc5. Length-dependent stimulation of condensation
took place during anaphase and depended on aurora/Ipl1 activity, its
localization to the spindle midzone, and phosphorylation of histone H3 on
Ser10, a known Ipl1 substrate. The anaphase spindle therefore may function
as a ruler to adapt the condensation of chromosomes to spindle length.
Consistent with this, chromosome condensation levels correlate with the
length of anaphase spindles
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.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/nto 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-2012-020