scholarly journals Centromere fragmentation is a common mitotic defect of S and G2checkpoint override

Cell Cycle ◽  
2013 ◽  
Vol 12 (10) ◽  
pp. 1588-1597 ◽  
Author(s):  
Neil Beeharry ◽  
Jerome Rattner ◽  
Juliane Caviston ◽  
Tim Yen
Keyword(s):  
Mitotic Defect

scholarly journals DPYSL3 modulates mitosis, migration, and epithelial-to-mesenchymal transition in claudin-low breast cancer

2018 ◽  
Vol 115 (51) ◽  
pp. E11978-E11987 ◽  
Author(s):  
Ryoichi Matsunuma ◽  
Doug W. Chan ◽  
Beom-Jun Kim ◽  
Purba Singh ◽  
Airi Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Negative Feedback ◽  
Epithelial To Mesenchymal Transition ◽  
Triple Negative ◽  
Breast Cancers ◽  
Mesenchymal Transition ◽  
Multinucleated Cells ◽  
P21 Activated Kinase ◽  
Emt Markers ◽  
Mitotic Defect

A Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomic analysis prioritized dihydropyrimidinase-like-3 (DPYSL3) as a multilevel (RNA/protein/phosphoprotein) expression outlier specific to the claudin-low (CLOW) subset of triple-negative breast cancers. A PubMed informatics tool indicated a paucity of data in the context of breast cancer, which further prioritized DPYSL3 for study. DPYSL3 knockdown in DPYSL3-positive (DPYSL3+) CLOW cell lines demonstrated reduced proliferation, yet enhanced motility and increased expression of epithelial-to-mesenchymal transition (EMT) markers, suggesting that DPYSL3 is a multifunctional signaling modulator. Slower proliferation in DPYSL3-negative (DPYSL3−) CLOW cells was associated with accumulation of multinucleated cells, indicating a mitotic defect that was associated with a collapse of the vimentin microfilament network and increased vimentin phosphorylation. DPYSL3 also suppressed the expression of EMT regulators SNAIL and TWIST and opposed p21 activated kinase 2 (PAK2)-dependent migration. However, these EMT regulators in turn induce DPYSL3 expression, suggesting that DPYSL3 participates in negative feedback on EMT. In conclusion, DPYSL3 expression identifies CLOW tumors that will be sensitive to approaches that promote vimentin phosphorylation during mitosis and inhibitors of PAK signaling during migration and EMT.

The SAC3 gene encodes a nuclear protein required for normal progression of mitosis

1996 ◽  
Vol 109 (6) ◽  
pp. 1575-1583
Author(s):  
A. Bauer ◽  
R. Kolling
Keyword(s):  
Cell Cycle ◽  
Actin Cytoskeleton ◽  
Nuclear Protein ◽  
Temperature Sensitive ◽  
Wild Type ◽  
Cell Cycle Delay ◽  
A Cell ◽  
Single Nucleus ◽  
Microtubule Function ◽  
Mitotic Defect

The SAC3 gene of Saccharomyces serevisiae has been implicated in actin function by genetic experiments showing that a temperature sensitive mutation in the essential actin gene (actl-1) can be suppressed by mutations in SAC3. An involvement of SAC3 in actin function is further suggested by the observation that the actin cytoskeleton is altered in SAC3 mutants. Our fractionation experiments, however, point to a nuclear localization of Sac3p. On sucrose density gradients Sac3p co-fractionated with the nuclear organelle markers examined. Furthermore, Sac3p was enriched 10-fold in a nuclei preparation along with the nuclear protein Nop1p. In this report we further show that SAC3 function is required for normal progression of mitosis. SAC3 mutants showed a higher fraction of large-budded cells in culture, indicative of a cell cycle delay. The predominant population among the large-budded sac3 cells were cells with a single nucleus at the bud-neck and a short intranuclear spindle. This suggests that a cell cycle delay occurs in mitosis prior to anaphase. The observation that SAC3 mutants lose chromosomes with higher frequency than wild-type is another indication for a mitotic defect in SAC3 mutants. We further noticed that SAC3 mutants are more resistant against the microtubule destabilizing drug benomyl. This finding suggests that SAC3 is involved, directly or indirectly, in microtubule function. In summary, our data indicate that SAC3 is involved in a process which affects both the actin cytoskeleton and mitosis.

Growth Suppression and Mitotic Defect Induced by JNJ-7706621, an Inhibitor of Cyclin-Dependent Kinases and Aurora Kinases

2012 ◽  
Vol 12 (6) ◽  
pp. 625-639 ◽  
Author(s):  
A. Matsuhashi ◽  
T. Ohno ◽  
M. Kimura ◽  
A. Hara ◽  
M. Saio ◽  
...  
Keyword(s):  
Growth Suppression ◽  
Aurora Kinases ◽  
Cyclin Dependent Kinases ◽  
Mitotic Defect

scholarly journals The Developmental Genetics of Hybrid Inviability: A Mitotic Defect in Drosophila Hybrids

Genetics ◽  
1997 ◽  
Vol 145 (4) ◽  
pp. 1031-1040 ◽  
Author(s):  
H Allen Orr ◽  
Laurence D Madden ◽  
Jerry A Coyne ◽  
Renee Goodwin ◽  
R Scott Hawley
Keyword(s):  
Chromatin Condensation ◽  
Mitotic Cell ◽  
Autosomal Gene ◽  
Developmental Genetics ◽  
Hybrid Male ◽  
Hybrid Inviability ◽  
Clonal Proliferation ◽  
Complete Failure ◽  
Mitotic Proliferation ◽  
Mitotic Defect

We report studies of the developmental basis of hybrid inviability in the Drosophila melanogaster complex. The pathology of these hybrids closely resembles that of mitotic mutants in D. melanogaster. We use mosaic and cytological analyses to show that hybrid male inviability is associated with, and probably caused by, a defect in mitotic cell division. In the mosaic study, we find that male clones produced in otherwise female hybrids are not cell lethal but are very small, probably reflecting defects in mitotic proliferation. Cytological inspection of larval neuroblasts reveals a profound mitotic defect in hybrids: chromosomes show a near-complete failure to condense even after 2 hr of incubation in colchicine. Both the defect in clonal proliferation and in chromatin condensation are rescued by mutations known to rescue normally inviable hybrid males. We present a simple model in which hybrid inviability is partly or entirely caused by a mitotic defect; this defect is, in turn, caused by an interaction between the Hybrid male rescue (Hmr) locus of D. melanogaster and autosomal gene(s) from D. melanogaster's sister species.

Loss of cap structure causes mitotic defect in Tetrahymena thermophila telomerase mutants

Chromosoma ◽  
2003 ◽  
Vol 111 (7) ◽  
pp. 429-437 ◽  
Author(s):  
Marina Petcherskaia ◽  
Jennifer M. McGuire ◽  
James M. Pherson ◽  
Karen E. Kirk
Keyword(s):  
Tetrahymena Thermophila ◽  
Mitotic Defect

scholarly journals HDAC1 Inactivation Induces Mitotic Defect and Caspase-Independent Autophagic Cell Death in Liver Cancer

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e34265 ◽  
Author(s):  
Hong Jian Xie ◽  
Ji Heon Noh ◽  
Jeong Kyu Kim ◽  
Kwang Hwa Jung ◽  
Jung Woo Eun ◽  
...  
Keyword(s):  
Cell Death ◽  
Liver Cancer ◽  
Autophagic Cell Death ◽  
Mitotic Defect

scholarly journals The Epstein-Barr Virus Immediate-Early Protein BZLF1 Induces both a G2 and a Mitotic Block

2002 ◽  
Vol 76 (19) ◽  
pp. 10030-10037 ◽  
Author(s):  
Amy Mauser ◽  
Elizabeth Holley-Guthrie ◽  
Dennis Simpson ◽  
William Kaufmann ◽  
Shannon Kenney
Keyword(s):  
Epstein Barr Virus ◽  
Cyclin B1 ◽  
Lytic Infection ◽  
Host Cells ◽  
Immediate Early ◽  
Barr Virus ◽  
Early Protein ◽  
Mitotic Block ◽  
Epstein Barr ◽  
Mitotic Defect

ABSTRACT The Epstein-Barr virus immediate-early protein BZLF1 is a transcriptional activator that mediates the switch from latent to lytic infection. Here we demonstrate that BZLF1 induces both a G2 block and a mitotic block in HeLa cells and inhibits chromosome condensation. While the G2 block is associated with decreased cyclin B1 in host cells and can be rescued by overexpression of cyclin B1, the mechanism for the mitotic defect is as yet undetermined.

scholarly journals Microcephaly models in the developing zebrafish retinal neuroepithelium point to an underlying defect in metaphase progression

Open Biology ◽  
2013 ◽  
Vol 3 (10) ◽  
pp. 130065 ◽  
Author(s):  
Claire Novorol ◽  
Janina Burkhardt ◽  
Kirstin J. Wood ◽  
Anila Iqbal ◽  
Claudio Roque ◽  
...  
Keyword(s):  
Brain Size ◽  
Time Lapse ◽  
Spindle Pole ◽  
Cellular Mechanisms ◽  
Proliferating Cells ◽  
Eye Size ◽  
Ideal System ◽  
Dramatic Rise ◽  
Autosomal Recessive Primary Microcephaly ◽  
Mitotic Defect

Autosomal recessive primary microcephaly (MCPH) is a congenital disorder characterized by significantly reduced brain size and mental retardation. Nine genes are currently known to be associated with the condition, all of which encode centrosomal or spindle pole proteins. MCPH is associated with a reduction in proliferation of neural progenitors during fetal development. The cellular mechanisms underlying the proliferation defect, however, are not fully understood. The zebrafish retinal neuroepithelium provides an ideal system to investigate this question. Mutant or morpholino-mediated knockdown of three known MCPH genes ( stil , aspm and wdr62 ) and a fourth centrosomal gene, odf2 , which is linked to several MCPH proteins, results in a marked reduction in head and eye size. Imaging studies reveal a dramatic rise in the fraction of proliferating cells in mitosis in all cases, and time-lapse microscopy points to a failure of progression through prometaphase. There was also increased apoptosis in all the MCPH models but this appears to be secondary to the mitotic defect as we frequently saw mitotically arrested cells disappear, and knocking down p53 apoptosis did not rescue the mitotic phenotype, either in whole retinas or clones.

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