Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Relationship of spindle assembly checkpoint fidelity to species body mass, lifespan, and developmental rate.

ABSTRACT: We have examined the tolerance of the spindle assembly checkpoint (SAC), as measured by the appearance of tetraploid cells in the presence of a microtubule inhibitor, in a series of primary cell strains derived from species with diverse lifespan and body size. We find that the integrity of the SAC varies among these species. There is a robust correlation between the integrity of the SAC and body size, but poor correlation with longevity and parameters of species development (i.e., time of female fertility, gestation length, and postnatal growth rate). The results suggest that fidelity of the SAC co-evolved more closely with the number of mitoses needed to reach adulthood than with species lifespan.

SUBMITTER: Lorenzini A

PROVIDER: S-EPMC3273901 | biostudies-other | 2011 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Relationship of spindle assembly checkpoint fidelity to species body mass, lifespan, and developmental rate.

Lorenzini Antonello A Fink Lauren S LS Stamato Thomas T Torres Claudio C Sell Christian C

Aging 20111201 12

We have examined the tolerance of the spindle assembly checkpoint (SAC), as measured by the appearance of tetraploid cells in the presence of a microtubule inhibitor, in a series of primary cell strains derived from species with diverse lifespan and body size. We find that the integrity of the SAC varies among these species. There is a robust correlation between the integrity of the SAC and body size, but poor correlation with longevity and parameters of species development (i.e., time of female ...[more]

PMID: 22201071

Similar Datasets

Absence of the Spindle Assembly Checkpoint Restores Mitotic Fidelity upon Loss of Sister Chromatid Cohesion.

Project description:The fidelity of mitosis depends on cohesive forces that keep sister chromatids together. This is mediated by cohesin that embraces sister chromatid fibers from the time of their replication until the subsequent mitosis [1-3]. Cleavage of cohesin marks anaphase onset, where single chromatids are dragged to the poles by the mitotic spindle [4-6]. Cohesin cleavage should only occur when all chromosomes are properly bio-oriented to ensure equal genome distribution and prevent random chromosome segregation. Unscheduled loss of sister chromatid cohesion is prevented by a safeguard mechanism known as the spindle assembly checkpoint (SAC) [7, 8]. To identify specific conditions capable of restoring defects associated with cohesion loss, we screened for genes whose depletion modulates Drosophila wing development when sister chromatid cohesion is impaired. Cohesion deficiency was induced by knockdown of the acetyltransferase separation anxiety (San)/Naa50, a cohesin complex stabilizer [9-12]. Several genes whose function impacts wing development upon cohesion loss were identified. Surprisingly, knockdown of key SAC proteins, Mad2 and Mps1, suppressed developmental defects associated with San depletion. SAC impairment upon cohesin removal, triggered by San depletion or artificial removal of the cohesin complex, prevented extensive genome shuffling, reduced segregation defects, and restored cell survival. This counterintuitive phenotypic suppression was caused by an intrinsic bias for efficient chromosome biorientation at mitotic entry, coupled with slow engagement of error-correction reactions. Thus, in contrast to SAC's role as a safeguard mechanism for mitotic fidelity, removal of this checkpoint alleviates mitotic errors when sister chromatid cohesion is compromised.

| S-EPMC6191932 | biostudies-literature

The spindle assembly checkpoint and speciation.

Project description:A mechanism is proposed by which speciation may occur without the need to postulate geographical isolation of the diverging populations. Closely related species that occupy overlapping or adjacent ecological niches often have an almost identical genome but differ by chromosomal rearrangements that result in reproductive isolation. The mitotic spindle assembly checkpoint normally functions to prevent gametes with non-identical karyotypes from forming viable zygotes. Unless gametes from two individuals happen to undergo the same chromosomal rearrangement at the same place and time, a most improbable situation, there has been no satisfactory explanation of how such rearrangements can propagate. Consideration of the dynamics of the spindle assembly checkpoint suggest that chromosomal fission or fusion events may occur that allow formation of viable heterozygotes between the rearranged and parental karyotypes, albeit with decreased fertility. Evolutionary dynamics calculations suggest that if the resulting heterozygous organisms have a selective advantage in an adjoining or overlapping ecological niche from that of the parental strain, despite the reproductive disadvantage of the population carrying the altered karyotype, it may accumulate sufficiently that homozygotes begin to emerge. At this point the reproductive disadvantage of the rearranged karyotype disappears, and a single population has been replaced by two populations that are partially reproductively isolated. This definition of species as populations that differ from other, closely related, species by karyotypic changes is consistent with the classical definition of a species as a population that is capable of interbreeding to produce fertile progeny. Even modest degrees of reproductive impairment of heterozygotes between two related populations may lead to speciation by this mechanism, and geographical isolation is not necessary for the process.

| S-EPMC7224227 | biostudies-literature

The MEN mediates the effects of the spindle assembly checkpoint on Kar9-dependent spindle pole body inheritance in budding yeast.

Project description:Many asymmetrically dividing cells segregate the poles of the mitotic spindle non-randomly between their two daughters. In budding yeast, the protein Kar9 localizes almost exclusively to the astral microtubules emanating from the old spindle pole body (SPB) and promotes its movement toward the bud. Thereby, Kar9 orients the spindle relative to the division axis. Here, we show that beyond perturbing Kar9 distribution, activation of the spindle assembly checkpoint (SAC) randomizes SPB inheritance. Inactivation of the B-type cyclin Clb5 led to a SAC-dependent defect in Kar9 orientation and SPB segregation. Furthermore, unlike the Clb4-dependent pathway, the Clb5- and SAC-dependent pathways functioned genetically upstream of the mitotic exit network (MEN) in SPB specification and Kar9-dependent SPB inheritance. Together, our study indicates that Clb5 functions in spindle assembly and that the SAC controls the specification and inheritance of yeast SPBs through inhibition of the MEN.

| S-EPMC3442921 | biostudies-literature

Kinetic framework of spindle assembly checkpoint signalling.

Project description:The mitotic spindle assembly checkpoint (SAC) delays anaphase onset until all chromosomes have attached to both spindle poles. Here, we investigated SAC signalling kinetics in response to acute detachment of individual chromosomes using laser microsurgery. Most detached chromosomes delayed anaphase until they had realigned to the metaphase plate. A substantial fraction of cells, however, entered anaphase in the presence of unaligned chromosomes. We identify two mechanisms by which cells can bypass the SAC: first, single unattached chromosomes inhibit the anaphase-promoting complex/cyclosome (APC/C) less efficiently than a full complement of unattached chromosomes; second, because of the relatively slow kinetics of re-imposing APC/C inhibition during metaphase, cells were unresponsive to chromosome detachment up to several minutes before anaphase onset. Our study defines when cells irreversibly commit to enter anaphase and shows that the SAC signal strength correlates with the number of unattached chromosomes. Detailed knowledge about SAC signalling kinetics is important for understanding the emergence of aneuploidy and the response of cancer cells to chemotherapeutics targeting the mitotic spindle.

| S-EPMC4067996 | biostudies-literature

Deficient spindle assembly checkpoint in multiple myeloma.

Project description:Multiple myeloma (MM) is a hematological disease characterized by an abnormal accumulation of plasma cells in the bone marrow. These cells have frequent cytogenetic abnormalities including translocations of the immunoglobulin heavy chain gene and chromosomal gains and losses. In fact, a singular characteristic differentiating MM from other hematological malignancies is the presence of a high degree of aneuploidies. As chromosomal abnormalities can be generated by alterations in the spindle assembly checkpoint (SAC), the functionality of such checkpoint was tested in MM. When SAC components were analyzed in MM cell lines, the RNA levels of most of them were conserved. Nevertheless, the protein content of some key constituents was very low in several cell lines, as was the case of MAD2 or CDC20 in RPMI-8226 or RPMI-LR5 cells. The recovery of their cellular content did not substantially affect cell growth, but improved their ability to segregate chromosomes. Finally, SAC functionality was tested by challenging cells with agents disrupting microtubule dynamics. Most of the cell lines analyzed exhibited functional defects in this checkpoint. Based on the data obtained, alterations both in SAC components and their functionality have been detected in MM, pointing to this pathway as a potential target in MM treatment.

| S-EPMC3223182 | biostudies-literature

Reverse engineering of the spindle assembly checkpoint.

Project description:The Spindle Assembly Checkpoint (SAC) is an intracellular mechanism that ensures proper chromosome segregation. By inhibiting Cdc20, a co-factor of the Anaphase Promoting Complex (APC), the checkpoint arrests the cell cycle until all chromosomes are properly attached to the mitotic spindle. Inhibition of Cdc20 is mediated by a conserved network of interacting proteins. The individual functions of these proteins are well characterized, but understanding of their integrated function is still rudimentary. We here describe our attempts to reverse-engineer the SAC network based on gene deletion phenotypes. We begun by formulating a general model of the SAC which enables us to predict the rate of chromosomal missegregation for any putative set of interactions between the SAC proteins. Next the missegregation rates of seven yeast strains are measured in response to the deletion of one or two checkpoint proteins. Finally, we searched for the set of interactions that correctly predicted the observed missegregation rates of all deletion mutants. Remarkably, although based on only seven phenotypes, the consistent network we obtained successfully reproduces many of the known properties of the SAC. Further insights provided by our analysis are discussed.

| S-EPMC2714964 | biostudies-literature

Noise resistance in the spindle assembly checkpoint.

Project description:Genetically identical cells vary in the amount of expressed proteins even when growing under the same conditions. It is not yet clear how cellular information processing copes with such stochastic fluctuations in protein levels. Here we examine the capacity of the spindle assembly checkpoint to buffer temporal fluctuations in the expression of Cdc20, a critical checkpoint target whose activity is inhibited to prevent premature cell cycle progression. Using mathematical modeling, we demonstrate that the checkpoint can buffer significant fluctuations in Cdc20 production rate. Critical to this buffering capacity is the use of sequestering-based mechanism for inhibiting Cdc20, as apposed to inhibition by enhancing protein degradation. We propose that the design of biological networks is limited by the need to overcome noise in gene expression.

| S-EPMC1681502 | biostudies-literature

Xenopus oocyte meiosis lacks spindle assembly checkpoint control.

Project description:The spindle assembly checkpoint (SAC) functions as a surveillance mechanism to detect chromosome misalignment and to delay anaphase until the errors are corrected. The SAC is thought to control mitosis and meiosis, including meiosis in mammalian eggs. However, it remains unknown if meiosis in the eggs of nonmammalian vertebrate species is also regulated by SAC. Using a novel karyotyping technique, we demonstrate that complete disruption of spindle microtubules in Xenopus laevis oocytes did not affect the bivalent-to-dyad transition at the time oocytes are undergoing anaphase I. These oocytes also acquired the ability to respond to parthenogenetic activation, which indicates proper metaphase II arrest. Similarly, oocytes exhibiting monopolar spindles, via inhibition of aurora B or Eg5 kinesin, underwent monopolar anaphase on time and without additional intervention. Therefore, the metaphase-to-anaphase transition in frog oocytes is not regulated by SAC.

| S-EPMC3628510 | biostudies-literature

Mimicking Ndc80 phosphorylation triggers spindle assembly checkpoint signalling.

Project description:The protein kinase Mps1 is, among others, essential for the spindle assembly checkpoint (SAC). We found that Saccharomyces cerevisiae Mps1 interacts physically with the N-terminal domain of Ndc80 (Ndc80(1-257)), a constituent of the Ndc80 kinetochore complex. Furthermore, Mps1 effectively phosphorylates Ndc80(1-257) in vitro and facilitates Ndc80 phosphorylation in vivo. Mutating 14 of the phosphorylation sites to alanine results in compromised checkpoint signalling upon nocodazole treatment of mutants. Mutating the identical sites to aspartate (to simulate constitutive phosphorylation) causes a metaphase arrest with wild-type-like bipolar kinetochore-microtubule attachment. This arrest is due to a constitutively active SAC and consequently the inviable aspartate mutant can be rescued by disrupting SAC signalling. Therefore, we conclude that a putative Mps1-dependent phosphorylation of Ndc80 is important for SAC activation at kinetochores.

| S-EPMC2683709 | biostudies-literature

ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint.

Project description:The spindle assembly checkpoint (SAC) ensures the fidelity of chromosome segregation during mitosis. Here, we show that ULK1, a serine/threonine kinase that plays a key role in initiation of autophagy, also has an important function in the activation of SAC. ULK1 phosphorylates the SAC protein Mad1 at Ser546 to recruit Mad1 to kinetochores. Furthermore, Rod/ZW10/Zwilch (RZZ) complex may serve as a receptor for phos-Ser546-Mad1 at kinetochore, since phosphorylation of Mad1 by ULK1 strengthens the interaction between Mad1 and RZZ complex. In addition, deletion of ULK1 increases chromosome instability and cytotoxicity of paclitaxel, resulting in significant impairment of cancer cell growth. These findings highlight the role of ULK1 as a protein kinase controlling the fidelity of chromosome segregation and cell-cycle progression.

| S-EPMC6736072 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data