Spindle Architectural Features Must Be Considered Along With Cell Size to Explain the Timing of Mitotic Checkpoint Silencing

Bloomfield, Mathew; Chen, Jing; Cimini, Daniela

doi:10.3389/fphys.2020.596263

Front. Physiol.

2021

DOI: 10.3389/fphys.2020.596263

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Spindle Architectural Features Must Be Considered Along With Cell Size to Explain the Timing of Mitotic Checkpoint Silencing

Mathew Bloomfield

¹

,

Jing Chen

²

,

Daniela Cimini

³

Abstract: Mitosis proceeds through a defined series of events that is largely conserved, but the amount of time needed for their completion can vary in different cells and organisms. In many systems, mitotic duration depends on the time required to satisfy and silence the spindle assembly checkpoint (SAC), also known as the mitotic checkpoint. Because SAC silencing involves trafficking SAC molecules among kinetochores, spindle, and cytoplasm, the size and geometry of the spindle relative to cell volume are expected to a… Show more

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Cited by 14 publications

(37 citation statements)

References 121 publications

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“…Our work sheds light on a link between variations in cell and nuclear size and the fitness of 4N cancer cells. Consistent with our earlier study (13), we found that cell and nuclear size do not always scale with genome size after WGD in colorectal and breast cancer cell lines, independent of p53 status. Functional assays revealed that the S 4N clones are more fit and tumorigenic than the L 4N clones, which can be attributed to the high rate of chromosome missegregation and inability to scale biosynthesis with size in the L 4N clones.…”

Section: Discussionsupporting

confidence: 92%

“…Specifically, the L 4N cells displayed the highest rates of both misaligned chromosomes and anaphase lagging chromosomes. Our previous study demonstrated that smaller 4N cells become rounder during mitosis than larger 4N cells (13).…”

Section: Discussionmentioning

confidence: 91%

“…Specifically, the L 4N cells displayed the highest rates of both misaligned chromosomes and anaphase lagging chromosomes. Our previous study demonstrated that smaller 4N cells become rounder during mitosis than larger 4N cells (13). Since mitotic rounding is biophysically favorable for spindle assembly and chromosome capture (64), inefficient cell rounding along with a larger cytoplasmic volume may hinder chromosome alignment and, in turn, promote chromosome missegregation in the L 4N clones.…”

Section: Discussionmentioning

confidence: 93%

“…8A-C), suggesting that they are more prone to chromosome missegregation than the S 4N clones and 2N cells. Our prior work showed that L 4N DLD1 displayed higher rates of misaligned chromosomes compared to S 4N DLD1 clones (13), a defect that can lead to chromosome missegregation when unresolved prior to anaphase onset (47,48). Consistent with this, we found that chromosome misalignment was highest in the L 4N clones across all cell lines (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Cell and nuclear size are associated with chromosomal instability and tumorigenicity in cancer cells that undergo whole genome doubling

Bloomfield

¹

,

Huth

²

,

McCausland

³

et al. 2025

Preprint

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1

0

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…Our work sheds light on a link between variations in cell and nuclear size and the fitness of 4N cancer cells. Consistent with our earlier study (13), we found that cell and nuclear size do not always scale with genome size after WGD in colorectal and breast cancer cell lines, independent of p53 status. Functional assays revealed that the S 4N clones are more fit and tumorigenic than the L 4N clones, which can be attributed to the high rate of chromosome missegregation and inability to scale biosynthesis with size in the L 4N clones.…”

Section: Discussionsupporting

confidence: 92%

“…Specifically, the L 4N cells displayed the highest rates of both misaligned chromosomes and anaphase lagging chromosomes. Our previous study demonstrated that smaller 4N cells become rounder during mitosis than larger 4N cells (13).…”

Section: Discussionmentioning

confidence: 91%

“…Specifically, the L 4N cells displayed the highest rates of both misaligned chromosomes and anaphase lagging chromosomes. Our previous study demonstrated that smaller 4N cells become rounder during mitosis than larger 4N cells (13). Since mitotic rounding is biophysically favorable for spindle assembly and chromosome capture (64), inefficient cell rounding along with a larger cytoplasmic volume may hinder chromosome alignment and, in turn, promote chromosome missegregation in the L 4N clones.…”

Section: Discussionmentioning

confidence: 93%

“…8A-C), suggesting that they are more prone to chromosome missegregation than the S 4N clones and 2N cells. Our prior work showed that L 4N DLD1 displayed higher rates of misaligned chromosomes compared to S 4N DLD1 clones (13), a defect that can lead to chromosome missegregation when unresolved prior to anaphase onset (47,48). Consistent with this, we found that chromosome misalignment was highest in the L 4N clones across all cell lines (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Cell and nuclear size are associated with chromosomal instability and tumorigenicity in cancer cells that undergo whole genome doubling

Bloomfield

¹

,

Huth

²

,

McCausland

³

et al. 2025

Preprint

Self Cite

1

0

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…We showed that cell and nuclear size as well as spindle geometry and composition did not consistently change in tetraploid clones relative to the diploid parental cells (Bloomfield et al, 2021). Relatively subtle differences in spindle architecture and cell size between tetraploid cells affected multiple mitotic events, including cell rounding, chromosome alignment, and mitotic timing (Bloomfield et al, 2021). A recent study found that large chromosomes near the periphery of the nucleus were more likely to end up near or behind a spindle pole during prometaphase and to be missegregated later in mitosis compared to chromosomes more centrally located in the nucleus (Klaasen et al, 2022).…”

Section: Figurementioning

confidence: 83%

The fate of extra centrosomes in newly formed tetraploid cells: should I stay, or should I go?

Bloomfield

¹

,

Cimini

²

2023

Front. Cell Dev. Biol.

Self Cite

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

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