Core Concepts
Centrosomes provide a "timely two-ness" to mitotic spindle organization that allows cell division to occur without a spindle assembly checkpoint (SAC)-dependent mitotic delay.
Abstract
The content examines the role of the spindle assembly checkpoint (SAC) in regulating mitosis in the absence of centrosomes. Key findings:
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Mitotic elongation in acentrosomal cells is dependent on MPS1 kinase activity, a key SAC component. Inhibition of MPS1 leads to premature mitotic exit and division failure in acentrosomal cells.
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The mitotic delay mediated by the SAC is necessary for successful cell division in acentrosomal cells. Prolonging mitosis through APC/C inhibition can rescue the division failure caused by MPS1 inhibition in acentrosomal cells.
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Polyploidy alone is not sufficient to cause the division failure phenotype observed with MPS1 inhibition in acentrosomal cells.
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Centrosomes facilitate the rapid establishment of bipolar spindle organization early in mitosis. This "timely two-ness" provided by centrosomes allows cell division to occur without the need for a SAC-dependent mitotic delay.
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Preventing centrosome separation, even in cells with centrosomes, is sufficient to make cell division reliant on a SAC-dependent mitotic delay, similar to acentrosomal cells.
In summary, the content demonstrates that centrosomes play a key role in coordinating the temporal organization of mitosis, allowing cell division to proceed efficiently even in the absence of a SAC-mediated delay.
Stats
"Acentriolar RPE-1 cells were generated in TP53-/- background, since RPE-1 cells with intact p53 pathways undergo G1 arrest in absence of centrioles."
"RPE-1 TP53-/- and U2OS cells treated with centrinone showed significant increases in acentrosomal cells as compared to DMSO controls, as did TP53-/-; SASS6-/- cells in comparison to TP53-/-cells as measured by number of γ-tubulin and centrin-3 co-positive puncta, which respectively mark PCM and centrioles."
"The time from nuclear envelope breakdown (NEBD) through anaphase onset was elongated in acentrosomal cells, while the duration of anaphase through cytokinesis was not significantly different compared to their appropriate controls."
"Both control and acentriolar cells treated with CFI-402257 showed reduced mitotic durations."
"The majority of control cells treated with CFI-402257 underwent bipolar mitoses, the majority of acentriolar cells treated with CFI-402257 rounded up and spread back out, producing a single mononucleate daughter cell."
"Acentrosomal cells treated with both proTAME and CFI-402257 eventually went on to divide, after the prolonged mitotic arrest."
"Polyploid cells with centrosomes did not require a SAC-based delay to divide when treated with CFI-402257."
"Control cells had two tubulin-dense MTOCs visible before NEBD, acentrosomal cells only established two MTOCs well after NEBD and chromosome condensation."
"Cells treated with both STLC and CFI-402257 formed monopolar spindles but then exited from mitosis, resulting in asymmetric division with extruded chromosomes."
Quotes
"The mitotic delay in acentrosomal cells is enforced by the SAC in a MPS1-dependent manner, and that a SAC-dependent mitotic delay is required for bipolar cell division to occur in acentrosomal cells."
"Prevention of centrosome separation suffices to make cell division reliant on a SAC-dependent mitotic delay."
"Centrosomes and their definition of two spindle poles early in mitosis provide a "timely two-ness" that allows cell division to occur in absence of a SAC-dependent mitotic delay."