scholarly journals Deregulation of HMGA1 expression induces chromosome instability through regulation of spindle assembly checkpoint genes

Oncotarget ◽  
2015 ◽  
Vol 6 (19) ◽  
pp. 17342-17353 ◽  
Author(s):  
Giovanna Maria Pierantoni ◽  
Andrea Conte ◽  
Cinzia Rinaldo ◽  
Mara Tornincasa ◽  
Raffaele Gerlini ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Chromosome Instability ◽  
Spindle Assembly ◽  
Hmga1 Expression ◽  
Checkpoint Genes

A Screen for Dynein Synthetic Lethals in Aspergillus nidulans Identifies Spindle Assembly Checkpoint Genes and Other Genes Involved in Mitosis

Genetics ◽  
1998 ◽  
Vol 149 (1) ◽  
pp. 101-116
Author(s):  
Vladimir P Efimov ◽  
N Ronald Morris
Keyword(s):  
Aspergillus Nidulans ◽  
Spindle Assembly Checkpoint ◽  
Genetic Interaction ◽  
Synthetic Lethality ◽  
Spindle Assembly ◽  
Nuclear Migration ◽  
Cytoplasmic Dynein ◽  
Vesicle Transport ◽  
Synthetic Lethal ◽  
Checkpoint Genes

Abstract Cytoplasmic dynein is a ubiquitously expressed microtubule motor involved in vesicle transport, mitosis, nuclear migration, and spindle orientation. In the filamentous fungus Aspergillus nidulans, inactivation of cytoplasmic dynein, although not lethal, severely impairs nuclear migration. The role of dynein in mitosis and vesicle transport in this organism is unclear. To investigate the complete range of dynein function in A. nidulans, we searched for synthetic lethal mutations that significantly reduced growth in the absence of dynein but had little effect on their own. We isolated 19 sld (synthetic lethality without dynein) mutations in nine different genes. Mutations in two genes exacerbate the nuclear migration defect seen in the absence of dynein. Mutations in six other genes, including sldA and sldB, show a strong synthetic lethal interaction with a mutation in the mitotic kinesin bimC and, thus, are likely to play a role in mitosis. Mutations in sldA and sldB also confer hypersensitivity to the microtubule-destabilizing drug benomyl. sldA and sldB were cloned by complementation of their mutant phenotypes using an A. nidulans autonomously replicating vector. Sequencing revealed homology to the spindle assembly checkpoint genes BUB1 and BUB3 from Saccharomyces cerevisiae. Genetic interaction between dynein and spindle assembly checkpoint genes, as well as other mitotic genes, indicates that A. nidulans dynein plays a role in mitosis. We suggest a model for dynein motor action in A. nidulans that can explain dynein involvement in both mitosis and nuclear distribution.

scholarly journals Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are infrequent in familial colorectal cancer and polyposis

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Pilar Mur ◽  
Richarda M. De Voer ◽  
Rubén Olivera-Salguero ◽  
Sandra Rodríguez-Perales ◽  
Tirso Pons ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Germline Mutations ◽  
Familial Colorectal Cancer ◽  
Checkpoint Genes

The S. pombe zfs1 gene is required to prevent septation if mitotic progression is inhibited

1999 ◽  
Vol 112 (18) ◽  
pp. 3103-3114 ◽  
Author(s):  
N. Beltraminelli ◽  
M. Murone ◽  
V. Simanis
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Chromosome Loss ◽  
Loss Of Function ◽  
Mitotic Progression ◽  
Septum Formation ◽  
Cell Cleavage ◽  
Multicopy Suppressors ◽  
Checkpoint Genes ◽  
Normal Mitosis

Schizosaccharomyces pombe cdc16p is required to limit the cell to forming a single division septum per cell cycle; the heat-sensitive loss-of-function mutant cdc16-116 completes mitosis, and then undergoes multiple rounds of septum formation without cell cleavage. cdc16p is a homologue of Saccharomyces cerevisiae BUB2p, and has also been implicated in the spindle assembly checkpoint function in S. pombe. To identify other proteins involved in regulating septum formation, we have screened for multicopy suppressors of the cdc16-116 mutation. In this paper, we describe one of these suppressors, zfs1. The null allele (zfs1-D1) is viable. However, at low temperatures it divides at a reduced size, while at higher temperatures, it partially suppresses heat sensitive mutants in genes signalling the onset of septum formation. Zfs1-D1 cells show an increased rate of chromosome loss during exponential growth. Moreover, if assembly of the spindle is prevented, zfs1-D1 cells do not arrest normally, but the activity of cdc2p kinase decays, and cells form a division septum without completing a normal mitosis. We conclude that zfs1 function is required to prevent septum formation and exit from mitosis if the mitotic spindle is not assembled. The suppression of cdc16-116 by zfs1 is independent of dma1 function and the spindle assembly checkpoint genes mad2 and mph1. The genetic interactions of zfs1 with genes regulating septum formation suggest that it may be a modulator of the signal transduction network controlling the onset of septum formation and exit from mitosis.

Germline Mutations in the Spindle Assembly Checkpoint Genes BUB1 and BUB3 Are Risk Factors for Colorectal Cancer

2013 ◽  
Vol 145 (3) ◽  
pp. 544-547 ◽  
Author(s):  
Richarda M. de Voer ◽  
Ad Geurts van Kessel ◽  
Robbert D.A. Weren ◽  
Marjolijn J.L. Ligtenberg ◽  
Dominique Smeets ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Germline Mutations ◽  
Checkpoint Genes

scholarly journals ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint

2019 ◽  
Vol 47 (15) ◽  
pp. 8096-8110 ◽  
Author(s):  
Fengjie Yuan ◽  
Ximin Jin ◽  
Dan Li ◽  
Yuanshuai Song ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Spindle Assembly Checkpoint ◽  
Chromosome Instability ◽  
Spindle Assembly ◽  
Cancer Cell Growth ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Significant Impairment

Abstract 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.

An α-Tubulin Mutant Demonstrates Distinguishable Functions Among the Spindle Assembly Checkpoint Genes in Saccharomyces cerevisiae

Genetics ◽  
2002 ◽  
Vol 161 (3) ◽  
pp. 983-994
Author(s):  
Katharine C Abruzzi ◽  
Margaret Magendantz ◽  
Frank Solomon
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mutant Allele ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Kinase Domain ◽  
Mitotic Checkpoint ◽  
Cold Sensitivity ◽  
Cold Sensitive ◽  
Checkpoint Genes

Abstract Cells expressing a mutant allele of α-tubulin, tub1-729, are cold sensitive and arrest as large-budded cells with microtubule defects. The cold sensitivity of tub1-729 is suppressed by extra copies of a subset of the mitotic checkpoint genes BUB1, BUB3, and MPS1, but not MAD1, MAD2, and MAD3. This suppression by checkpoint genes does not depend upon their role in the MAD2-dependent spindle assembly checkpoint. In addition, BUB1 requires an intact kinase domain as well as Bub3p to suppress tub1-729. The data suggest that tub1-729 cells are defective in microtubule-kinetochore attachments and that the products of specific checkpoint genes can act either directly or indirectly to affect these attachments.

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