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Checkpoint genes required to delay cell division in response to nocodazole respond to impaired kinetochore function in the yeast Saccharomyces cerevisiae
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The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores
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of outstanding interest. Applying tension with a microneedle at the kinetochore of a chromosome overrides checkpoint-induced delays in anaphase. This paper and [28] provide the most compelling evidence that lack of tension is the trait monitored by the spindle assembly checkpoint.
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Toyn JH, Johnson AL, Johnston LH. Segregation of unreplicated chromosomes in Saccharomyces cerevisiae reveals a novel G1/M-phase checkpoint. of special interest Mol Cell Biol. 15:1995;5312-5321 This paper and [22] show that S. cerevisiae containing certain cdc6 and cdc7 mutations, which result in a failure to replicate chromosomes, still go through mitosis with no delay. This observation suggests that lack of tension at kinetochores in budding yeast does not activate the spindle assembly checkpoint.
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Cdc6 is an unstable protein whose de novo synthesis in G1 is important for the onset of S phase and for preventing a reductional anaphase in the budding yeast Saccharomyces cerevisiae
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0029146196
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Kinetochore chemistry is sensitive to tension and may link mitotic forces to a cell cycle checkpoint
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of outstanding interest. Kinetochores that are not under tension stain brightly with the antibody 3F3/2. This staining is reduced when tension is applied to these kinetochores with a microneedle. This result suggests that defects in kinetochore attachment to the spindle and a lack of tension at the kinetochore are detected by the same components, and may even reflect the same defect.
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Nicklas RB, Ward SC, Gorbsky GJ. Kinetochore chemistry is sensitive to tension and may link mitotic forces to a cell cycle checkpoint. of outstanding interest J Cell Biol. 130:1995;929-939 Kinetochores that are not under tension stain brightly with the antibody 3F3/2. This staining is reduced when tension is applied to these kinetochores with a microneedle. This result suggests that defects in kinetochore attachment to the spindle and a lack of tension at the kinetochore are detected by the same components, and may even reflect the same defect.
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Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores
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labeled epitope, localizes to kinetochores that have attached to the spindle. This paper provides the first evidence that checkpoint components are conserved from yeast to vertebrates, and also suggests that the budding yeast checkpoint components may reside at the kinetochore too. of outstanding interest
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Mad1p, a phosphoprotein component of the spindle assembly checkpoint in budding yeast
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of outstanding interest. of special interest. This paper describes the cloning of MAD1 and its interesting localization, and shows that Mad1 is hyperphosphorylated when the checkpoint is activated. Mad1 hyperphosphorylation requires BUB1, BUB3 and MAD2, but not BUB2 and MAD3. A crude biochemical pathway can be created from these data and those found in [9].
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of outstanding interest Hardwick K, Murray AW. Mad1p, a phosphoprotein component of the spindle assembly checkpoint in budding yeast. of special interest J Cell Biol. 131:1995;709-720 This paper describes the cloning of MAD1 and its interesting localization, and shows that Mad1 is hyperphosphorylated when the checkpoint is activated. Mad1 hyperphosphorylation requires BUB1, BUB3 and MAD2, but not BUB2 and MAD3. A crude biochemical pathway can be created from these data and those found in [9].
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Cross SM, Sanchez CA, Morgan CA, Schimke MK, Ramel S, Idzerda RL, Raskind WH, Reid BJ. A p53-dependent mouse spindle checkpoint. of special interest Science. 267:1995;1353-1356 This paper suggests that p53 is a component of the spindle assembly checkpoint in animal cells. Note that both wild-type and p53-mutant cells arrest poorly in nocodazole, suggesting that a different checkpoint defect may lead to the increase in ploidy of the p53-deficient cells.
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Pds1p, an inhibitor of anaphase in budding yeast, plays a critical role in the APC And checkpoint pathway(s)
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of special interest. This paper and [43] identify Pds1 as a protein that regulates sister chromatid separation. pds1 mutants prematurely separate their sister chromatids, and have defects in the DNA-damage checkpoint and in spindle elongation. As expected, the Pds1 protein is degraded as cells exist mitosis and contains a putative cyclin-destruction box.
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Yamamoto YA, Guacci V, Koshland D. Pds1p, an inhibitor of anaphase in budding yeast, plays a critical role in the APC And checkpoint pathway(s). of special interest J Cell Biol. 133:1996;99-110 This paper and [43] identify Pds1 as a protein that regulates sister chromatid separation. pds1 mutants prematurely separate their sister chromatids, and have defects in the DNA-damage checkpoint and in spindle elongation. As expected, the Pds1 protein is degraded as cells exist mitosis and contains a putative cyclin-destruction box.
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