scholarly journals Loss of Mitotic Spindle Checkpoint Activity Predisposes to Chromosomal Instability at Early Stages of Fibrosarcoma Development

Cell Cycle ◽  
2003 ◽  
Vol 2 (3) ◽  
pp. 237-241 ◽  
Author(s):  
Duncan M. Gascoyne ◽  
Mary L. Hixon ◽  
Antonio Gualberto ◽  
Maria d.M. Vivanco
Keyword(s):  
Mitotic Spindle ◽  
Chromosomal Instability ◽  
Spindle Checkpoint ◽  
Mitotic Spindle Checkpoint ◽  
Early Stages

scholarly journals Variable Levels of Chromosomal Instability and Mitotic Spindle Checkpoint Defects in Breast Cancer

2002 ◽  
Vol 161 (2) ◽  
pp. 391-397 ◽  
Author(s):  
Dae-Sung Yoon ◽  
Robert P. Wersto ◽  
Weibo Zhou ◽  
Francis J. Chrest ◽  
Elizabeth S. Garrett ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mitotic Spindle ◽  
Chromosomal Instability ◽  
Spindle Checkpoint ◽  
Mitotic Spindle Checkpoint

Characterization of MAD2B and Other Mitotic Spindle Checkpoint Genes

Genomics ◽  
1999 ◽  
Vol 58 (2) ◽  
pp. 181-187 ◽  
Author(s):  
Daniel P. Cahill ◽  
Luis T. da Costa ◽  
Eleanor B. Carson-Walter ◽  
Kenneth W. Kinzler ◽  
Bert Vogelstein ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Checkpoint ◽  
Mitotic Spindle Checkpoint ◽  
Checkpoint Genes

scholarly journals The ESCRT protein Chmp4c regulates mitotic spindle checkpoint signaling

2018 ◽  
Vol 217 (3) ◽  
pp. 861-876 ◽  
Author(s):  
Eleni Petsalaki ◽  
Maria Dandoulaki ◽  
George Zachos
Keyword(s):  
Mitotic Spindle ◽  
Spindle Checkpoint ◽  
Metaphase Plate ◽  
Membrane Remodeling ◽  
Mitotic Progression ◽  
Mitotic Spindle Checkpoint ◽  
Checkpoint Signaling ◽  
Checkpoint Proteins ◽  
Endosomal Sorting ◽  
Anaphase Onset

The mitotic spindle checkpoint delays anaphase onset in the presence of unattached kinetochores, and efficient checkpoint signaling requires kinetochore localization of the Rod–ZW10–Zwilch (RZZ) complex. In the present study, we show that human Chmp4c, a protein involved in membrane remodeling, localizes to kinetochores in prometaphase but is reduced in chromosomes aligned at the metaphase plate. Chmp4c promotes stable kinetochore–microtubule attachments and is required for proper mitotic progression, faithful chromosome alignment, and segregation. Depletion of Chmp4c diminishes localization of RZZ and Mad1-Mad2 checkpoint proteins to prometaphase kinetochores and impairs mitotic arrest when microtubules are depolymerized by nocodazole. Furthermore, Chmp4c binds to ZW10 through a small C-terminal region, and constitutive Chmp4c kinetochore targeting causes a ZW10-dependent checkpoint metaphase arrest. In addition, Chmp4c spindle functions do not require endosomal sorting complex required for transport–dependent membrane remodeling. These results show that Chmp4c regulates the mitotic spindle checkpoint by promoting localization of the RZZ complex to unattached kinetochores.

MonoallelicBUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome

2006 ◽  
Vol 140A (4) ◽  
pp. 358-367 ◽  
Author(s):  
Shinya Matsuura ◽  
Yoshiyuki Matsumoto ◽  
Ken-ichi Morishima ◽  
Hideki Izumi ◽  
Hiroshi Matsumoto ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Checkpoint ◽  
Mitotic Spindle Checkpoint

Mouse Hematopoietic Stem Cells, Unlike Human and Mouse Embryonic Stem Cells, Exhibit Checkpoint-Apoptosis Coupling.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3357-3357
Author(s):  
Sara Rohrabaugh ◽  
Charlie Mantel ◽  
Hal E. Broxmeyer
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Progenitor Cells ◽  
Mitotic Spindle ◽  
Flow Cytometric Analysis ◽  
Spindle Checkpoint ◽  
Embryonic Stem ◽  
Hematopoietic Stem ◽  
Mitotic Spindle Checkpoint

Abstract Cell cycle checkpoints guarantee that cells move through the events of the cell cycle in the appropriate manner. The mitotic spindle checkpoint, also known as the spindle assembly checkpoint (SAC), helps to ensure the proper segregation of chromosomes into daughter cells during mitosis. Our lab recently reported on the condition of the SAC in both mouse and human embryonic stem cells (ESCs). We found that ESCs do not initiate apoptosis when the SAC is activated, which allowed these cells to tolerate a polyploid state resulting from the aberrant mitosis (Mantel et al. Blood.109: 4518–4527. 2007). These results lead us to conclude that the spindle checkpoint is uncoupled from apoptosis in ESCs. Knowing whether adult tissue specific stem/progenitor cells, such as hematopoietic stem cells (HSCs), have checkpoints which are uncoupled from apoptosis is extremely important information. If HSCs were to manifest such checkpoint uncoupling as that which we defined for ESCs, this might present a problem for the ex-vivo expansion and transplantation of HSCs. Using multiparametric permeablized cell flow cytometric analysis, we found the mitotic spindle checkpoint to be functional in primary murine sca 1+/c-kit+/lin- cells (LSK cells), a population highly enriched in primitive hematopoietic stem/progenitor cells. Using nocodazole, which exerts its affect by depolymerizing microtubules, we were able to activate the spindle checkpoint in low density mononuclear cells collected from murine bone marrow. Through flow cytometric analysis of the LSK cells in the mononuclear fraction, we were able to determine that spindle checkpoint activation in LSK cells resulted in a cell cycle arrest in mitosis, which was determined by DNA content of the cells, and eventually this arrest lead to cell death via apoptosis, as indicated by caspase-3 activation. This behavior is unlike that of ESCs, which exit mitosis and become polyploidy after prolonged spindle checkpoint activation. Thus the mitotic spindle checkpoint appears to be coupled to apoptosis in this particular set of tissue specific stem/progenitor cells, which lessens the possibility that ex-vivo expansion of hematopoietic stem cells will result in abnormalities to these cells that may give rise to disease initiation or progression after their transplantation.

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