scholarly journals The spindle assembly checkpoint functions during early development in non-chordate embryos

2019 ◽  
Author(s):  
Janet Chenevert ◽  
Marianne Roca ◽  
Lydia Besnardeau ◽  
Antonella Ruggiero ◽  
Dalileh Nabi ◽  
...  
Keyword(s):  
Early Development ◽  
Spindle Assembly Checkpoint ◽  
Sea Urchins ◽  
Volume Ratio ◽  
Spindle Assembly ◽  
Eukaryotic Cells ◽  
Embryonic Cells ◽  
Checkpoint Response ◽  
Early Embryos ◽  
Spindle Microtubules

In eukaryotic cells, a spindle assembly checkpoint (SAC) ensures accurate chromosome segregation. This control mechanism monitors proper attachment of chromosomes to spindle microtubules and delays mitotic progression if connections are erroneous or absent. The SAC operates in all eukaryotic cells tested so far, but is thought to be relaxed during early embryonic development in animals. Here, we evaluate the checkpoint response to lack of kinetochore-spindle microtubule interactions in early embryos of diverse animal species from the main metazoan groups. Our analysis shows that there are two classes of embryos, either proficient or deficient for SAC activation during cleavage. Sea urchins, mussels and jellyfish embryos show a prolonged mitotic block in the absence of spindle microtubules from the first cleavage division, while ascidian and amphioxus embryos, like those of Xenopus and zebrafish, continue mitotic cycling without delay. SAC competence during early development shows no correlation with cell size, chromosome number or kinetochore to cell volume ratio, ruling out the hypothesis that lack of checkpoint activity in early embryos is due to the large egg volume. Our results instead indicate that there is no inherent incompatibility between SAC activity and large fast-dividing embryonic cells. We suggest that SAC proficiency is the default situation of metazoan embryos, and that SAC activity is specifically silenced in chordate species with fast dividing embryos.

scholarly journals The Spindle Assembly Checkpoint Functions during Early Development in Non-Chordate Embryos

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1087
Author(s):  
Janet Chenevert ◽  
Marianne Roca ◽  
Lydia Besnardeau ◽  
Antonella Ruggiero ◽  
Dalileh Nabi ◽  
...  
Keyword(s):  
Early Development ◽  
Spindle Assembly Checkpoint ◽  
Sea Urchins ◽  
Volume Ratio ◽  
Spindle Assembly ◽  
Mitotic Progression ◽  
Checkpoint Response ◽  
Ascidian Embryos ◽  
Spindle Microtubules ◽  
Prolonged Delay

In eukaryotic cells, a spindle assembly checkpoint (SAC) ensures accurate chromosome segregation, by monitoring proper attachment of chromosomes to spindle microtubules and delaying mitotic progression if connections are erroneous or absent. The SAC is thought to be relaxed during early embryonic development. Here, we evaluate the checkpoint response to lack of kinetochore-spindle microtubule interactions in early embryos of diverse animal species. Our analysis shows that there are two classes of embryos, either proficient or deficient for SAC activation during cleavage. Sea urchins, mussels, and jellyfish embryos show a prolonged delay in mitotic progression in the absence of spindle microtubules from the first cleavage division, while ascidian and amphioxus embryos, like those of Xenopus and zebrafish, continue mitotic cycling without delay. SAC competence during early development shows no correlation with cell size, chromosome number, or kinetochore to cell volume ratio. We show that SAC proteins Mad1, Mad2, and Mps1 lack the ability to recognize unattached kinetochores in ascidian embryos, indicating that SAC signaling is not diluted but rather actively silenced during early chordate development.

Evidence that the spindle assembly checkpoint does not regulate APCFzy activity in Drosophila female meiosis

Genome ◽  
2012 ◽  
Vol 55 (1) ◽  
pp. 63-67 ◽  
Author(s):  
Osamah Batiha ◽  
Andrew Swan
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Cyclin B ◽  
Meiotic Spindle ◽  
Loss Of Function ◽  
Female Meiosis ◽  
Chromosome Attachment ◽  
Spindle Microtubules ◽  
Made In

The spindle assembly checkpoint (SAC) plays an important role in mitotic cells to sense improper chromosome attachment to spindle microtubules and to inhibit APCFzy-dependent destruction of cyclin B and Securin; consequent initiation of anaphase until correct attachments are made. In Drosophila , SAC genes have been found to play a role in ensuring proper chromosome segregation in meiosis, possibly reflecting a similar role for the SAC in APCFzy inhibition during meiosis. We found that loss of function mutations in SAC genes, Mad2, zwilch, and mps1, do not lead to the predicted rise in APCFzy-dependent degradation of cyclin B either globally throughout the egg or locally on the meiotic spindle. Further, the SAC is not responsible for the inability of APCFzy to target cyclin B and promote anaphase in metaphase II arrested eggs from cort mutant females. Our findings support the argument that SAC proteins play checkpoint independent roles in Drosophila female meiosis and that other mechanisms must function to control APC activity.

scholarly journals PP2A-B56 opposes Mps1 phosphorylation of Knl1 and thereby promotes spindle assembly checkpoint silencing

2014 ◽  
Vol 206 (7) ◽  
pp. 833-842 ◽  
Author(s):  
Antonio Espert ◽  
Pelin Uluocak ◽  
Ricardo Nunes Bastos ◽  
Davinderpreet Mangat ◽  
Philipp Graab ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Mammalian Cells ◽  
Feedback Loop ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Eukaryotic Cells ◽  
Aurora B ◽  
Safeguard Mechanism

The spindle assembly checkpoint (SAC) monitors correct attachment of chromosomes to microtubules, an important safeguard mechanism ensuring faithful chromosome segregation in eukaryotic cells. How the SAC signal is turned off once all the chromosomes have successfully attached to the spindle remains an unresolved question. Mps1 phosphorylation of Knl1 results in recruitment of the SAC proteins Bub1, Bub3, and BubR1 to the kinetochore and production of the wait-anaphase signal. SAC silencing is therefore expected to involve a phosphatase opposing Mps1. Here we demonstrate in vivo and in vitro that BubR1-associated PP2A-B56 is a key phosphatase for the removal of the Mps1-mediated Knl1 phosphorylations necessary for Bub1/BubR1 recruitment in mammalian cells. SAC silencing is thus promoted by a negative feedback loop involving the Mps1-dependent recruitment of a phosphatase opposing Mps1. Our findings extend the previously reported role for BubR1-associated PP2A-B56 in opposing Aurora B and suggest that BubR1-bound PP2A-B56 integrates kinetochore surveillance and silencing of the SAC.

scholarly journals Aberrantly segregating centromeres activate the spindle assembly checkpoint in budding yeast.

1996 ◽  
Vol 133 (1) ◽  
pp. 75-84 ◽  
Author(s):  
W A Wells ◽  
A W Murray
Keyword(s):  
Copy Number ◽  
Spindle Assembly Checkpoint ◽  
Budding Yeast ◽  
Spindle Assembly ◽  
Pedigree Analysis ◽  
Eukaryotic Cells ◽  
Gene Products ◽  
Chromosome Behavior ◽  
Daughter Cells ◽  
Chromosome Alignment

The spindle assembly checkpoint is the mechanism or set of mechanisms that prevents cells with defects in chromosome alignment or spindle assembly from passing through mitosis. We have investigated the effects of mini-chromosomes on this checkpoint in budding yeast by performing pedigree analysis. This method allowed us to observe the frequency and duration of cell cycle delays in individual cells. Short, centromeric linear mini-chromosomes, which have a low fidelity of segregation, cause frequent delays in mitosis. Their circular counterparts and longer linear mini-chromosomes, which segregate more efficiently, show a much lower frequency of mitotic delays, but these delays occur much more frequently in divisions where the mini-chromosome segregates to only one of the two daughter cells. Using a conditional centromere to increase the copy number of a circular mini-chromosome greatly increases the frequency of delayed divisions. In all cases the division delays are completely abolished by the mad mutants that inactivate the spindle assembly checkpoint, demonstrating that the Mad gene products are required to detect the subtle defects in chromosome behavior that have been observed to arrest higher eukaryotic cells in mitosis.

scholarly journals Congressing kinetochores progressively load Ska complexes to prevent force-dependent detachment

2017 ◽  
Vol 216 (6) ◽  
pp. 1623-1639 ◽  
Author(s):  
Philip Auckland ◽  
Nicholas I. Clarke ◽  
Stephen J. Royle ◽  
Andrew D. McAinsh
Keyword(s):  
Bearing Capacity ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Live Cells ◽  
Load Bearing Capacity ◽  
Load Bearing ◽  
Naturally Occurring ◽  
Chromosome Congression ◽  
Spindle Microtubules

Kinetochores mediate chromosome congression by either sliding along the lattice of spindle microtubules or forming end-on attachments to their depolymerizing plus-ends. By following the fates of individual kinetochores as they congress in live cells, we reveal that the Ska complex is required for a distinct substep of the depolymerization-coupled pulling mechanism. Ska depletion increases the frequency of naturally occurring, force-dependent P kinetochore detachment events, while being dispensable for the initial biorientation and movement of chromosomes. In unperturbed cells, these release events are followed by reattachment and successful congression, whereas in Ska-depleted cells, detached kinetochores remain in a futile reattachment/detachment cycle that prevents congression. We further find that Ska is progressively loaded onto bioriented kinetochore pairs as they congress. We thus propose a model in which kinetochores mature through Ska complex recruitment and that this is required for improved load-bearing capacity and silencing of the spindle assembly checkpoint.

scholarly journals DNA damage responses in mammalian oocytes

Reproduction ◽  
2016 ◽  
Vol 152 (1) ◽  
pp. R15-R22 ◽  
Author(s):  
Josie K Collins ◽  
Keith T Jones
Keyword(s):  
Dna Damage ◽  
Spindle Assembly Checkpoint ◽  
Germinal Vesicle ◽  
Spindle Assembly ◽  
Stages Of Growth ◽  
Microtubule Attachment ◽  
Dna Damage Responses ◽  
Chromosome Attachment ◽  
Spindle Microtubules ◽  
Meiosis I

DNA damage acquired during meiosis can lead to infertility and miscarriage. Hence, it should be important for an oocyte to be able to detect and respond to such events in order to make a healthy egg. Here, the strategies taken by oocytes during their stages of growth to respond to DNA damaging events are reviewed. In particular, recent evidence of a novel pathway in fully grown oocytes helps prevent the formation of mature eggs with DNA damage. It has been found that fully grown germinal vesicle stage oocytes that have been DNA damaged do not arrest at this point in meiosis, but instead undergo meiotic resumption and stall during the first meiotic division. The Spindle Assembly Checkpoint, which is a well-known mitotic pathway employed by somatic cells to monitor chromosome attachment to spindle microtubules, appears to be utilised by oocytes also to respond to DNA damage. As such maturing oocytes are arrested at metaphase I due to an active Spindle Assembly Checkpoint. This is surprising given this checkpoint has been previously studied in oocytes and considered to be weak and ineffectual because of its poor ability to be activated in response to microtubule attachment errors. Therefore, the involvement of the Spindle Assembly Checkpoint in DNA damage responses of mature oocytes during meiosis I uncovers a novel second function for this ubiquitous cellular checkpoint.

scholarly journals Sustained Spindle-Assembly Checkpoint Response Requires De Novo Transcription and Translation of Cyclin B1

PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e13037 ◽  
Author(s):  
Ana Lúcia Mena ◽  
Eric W.-F. Lam ◽  
Sukalyan Chatterjee
Keyword(s):  
Spindle Assembly Checkpoint ◽  
De Novo ◽  
Spindle Assembly ◽  
Cyclin B1 ◽  
Checkpoint Response

scholarly journals Aurora Kinase-A Inactivates DNA Damage-Induced Apoptosis and Spindle Assembly Checkpoint Response Functions of p73

Cancer Cell ◽  
2012 ◽  
Vol 21 (2) ◽  
pp. 196-211 ◽  
Author(s):  
Hiroshi Katayama ◽  
Jin Wang ◽  
Warapen Treekitkarnmongkol ◽  
Hidehiko Kawai ◽  
Kaori Sasai ◽  
...  
Keyword(s):  
Dna Damage ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Aurora Kinase ◽  
Response Functions ◽  
Checkpoint Response ◽  
Aurora Kinase A ◽  
Induced Apoptosis ◽  
Kinase A

scholarly journals PRP4 is a spindle assembly checkpoint protein required for MPS1, MAD1, and MAD2 localization to the kinetochores

2007 ◽  
Vol 179 (4) ◽  
pp. 601-609 ◽  
Author(s):  
Emilie Montembault ◽  
Stéphanie Dutertre ◽  
Claude Prigent ◽  
Régis Giet
Keyword(s):  
Rna Processing ◽  
Mitotic Spindle ◽  
Messenger Rna ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Checkpoint Proteins ◽  
Checkpoint Protein ◽  
Anaphase Onset ◽  
Spindle Microtubules ◽  
Spindle Assembly Checkpoint Protein

The spindle checkpoint delays anaphase onset until every chromosome kinetochore has been efficiently captured by the mitotic spindle microtubules. In this study, we report that the human pre–messenger RNA processing 4 (PRP4) protein kinase associates with kinetochores during mitosis. PRP4 depletion by RNA interference induces mitotic acceleration. Moreover, we frequently observe lagging chromatids during anaphase leading to aneuploidy. PRP4-depleted cells do not arrest in mitosis after nocodazole treatment, indicating a spindle assembly checkpoint (SAC) failure. Thus, we find that PRP4 is necessary for recruitment or maintenance of the checkpoint proteins MPS1, MAD1, and MAD2 at the kinetochores. Our data clearly identify PRP4 as a previously unrecognized kinetochore component that is necessary to establish a functional SAC.

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