The spindle checkpoint monitors the interaction between spindle microtubules and kinetochores to prevent precocious entry into anaphase, delaying this stage of mitosis until all condensed chromosomes have been attached to the mitotic spindle in a bi-oriented manner (so that the two kinetochores associated with a pair of sister chromatids are oriented toward opposite poles of the spindle). In addition to conserved Bub and Mad family members, which are known to function in the spindle checkpoint pathway in organisms ranging from yeast to mammals, two mRNA transport genes, Rae1 and Nup9, are also involved in the spindle checkpoint function in mammals. Biochemically, activated spindle checkpoint components have been shown to suppress the activity of the anaphase promoting complex/cyclosome. It is generally thought that decreased activity of the checkpoint components predisposes cells to chromosomal instability, aneuploidy, and malignant transformation. Interestingly, a recent study has shed light on a new function of the spindle checkpoint components Bub3 and Rae1 in the regulation of aging. Mice with haploinsufficiency of Bub3 and Rae1 have a short life span that is associated with the early onset of aging-related features. The progeroid phenotypes caused by deficiency of Bub3 and Rae1 are tightly linked to precocious activation of cellular senescence, but not apoptotic, programs. Therefore, premature aging, rather than neoplastic transformation, may be the major manifestation of a compromised spindle checkpoint in vivo.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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