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.

scholarly journals Diverse Functions of Spindle Assembly Checkpoint Genes in Saccharomyces cerevisiae

Genetics ◽  
2005 ◽  
Vol 172 (1) ◽  
pp. 53-65 ◽  
Author(s):  
Jewel A. Daniel ◽  
Brice E. Keyes ◽  
Yvonne P. Y. Ng ◽  
C. Onyi Freeman ◽  
Daniel J. Burke
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
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

scholarly journals A tumor suppressor role of the Bub3 spindle checkpoint protein after apoptosis inhibition

2013 ◽  
Vol 201 (3) ◽  
pp. 385-393 ◽  
Author(s):  
Sara Morais da Silva ◽  
Tatiana Moutinho-Santos ◽  
Claudio E. Sunkel
Keyword(s):  
Tumor Suppressor ◽  
Spindle Assembly Checkpoint ◽  
Mitotic Checkpoint ◽  
Proliferative Potential ◽  
Altered Expression ◽  
Apoptosis Inhibition ◽  
Wing Imaginal Discs ◽  
A Minor ◽  
Checkpoint Genes

Most solid tumors contain aneuploid cells, indicating that the mitotic checkpoint is permissive to the proliferation of chromosomally aberrant cells. However, mutated or altered expression of mitotic checkpoint genes accounts for a minor proportion of human tumors. We describe a Drosophila melanogaster tumorigenesis model derived from knocking down spindle assembly checkpoint (SAC) genes and preventing apoptosis in wing imaginal discs. Bub3-deficient tumors that were also deficient in apoptosis displayed neoplastic growth, chromosomal aneuploidy, and high proliferative potential after transplantation into adult flies. Inducing aneuploidy by knocking down CENP-E and preventing apoptosis does not induce tumorigenesis, indicating that aneuploidy is not sufficient for hyperplasia. In this system, the aneuploidy caused by a deficient SAC is not driving tumorigenesis because preventing Bub3 from binding to the kinetochore does not cause hyperproliferation. Our data suggest that Bub3 has a nonkinetochore-dependent function that is consistent with its role as a tumor suppressor.

scholarly journals The Spindle Assembly Checkpoint Regulates the Phosphorylation State of a Subset of DNA Checkpoint Proteins in Saccharomyces cerevisiae

2006 ◽  
Vol 26 (24) ◽  
pp. 9149-9161 ◽  
Author(s):  
Céline Clémenson ◽  
Marie-Claude Marsolier-Kergoat
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Damage Response ◽  
Spindle Assembly Checkpoint ◽  
Spindle Checkpoint ◽  
Spindle Assembly ◽  
Dna Lesions ◽  
Checkpoint Proteins ◽  
Cell Responses ◽  
Spindle Assembly Checkpoints ◽  
Damage Response

ABSTRACT The DNA and the spindle assembly checkpoints play key roles in maintaining genomic integrity by coordinating cell responses to DNA lesions and spindle dysfunctions, respectively. These two surveillance pathways seem to operate mostly independently of one another, and little is known about their potential physiological connections. Here, we show that in Saccharomyces cerevisiae, the activation of the spindle assembly checkpoint triggers phosphorylation changes in two components of the DNA checkpoint, Rad53 and Rad9. These modifications are independent of the other DNA checkpoint proteins and are abolished in spindle checkpoint-defective mutants, hinting at specific functions for Rad53 and Rad9 in the spindle damage response. Moreover, we found that after UV irradiation, Rad9 phosphorylation is altered and Rad53 inactivation is accelerated when the spindle checkpoint is activated, which suggests the implication of the spindle checkpoint in the regulation of the DNA damage response.

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