Dual mechanisms regulate the recruitment of spindle assembly checkpoint proteins to the budding yeast kinetochore

Aravamudhan, Pavithra; Chen, Renjie; Roy, Babhrubahan; Sim, Janice; Joglekar, Ajit P.

doi:10.1091/mbc.e16-01-0007

Cited by 24 publications

(44 citation statements)

References 49 publications

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“…2B). This is consistent with our prior finding that Glc7 activity has little influence on Bub3 recruitment in unattached kinetochores (Aravamudhan et al, 2016). We next used flow cytometry to quantify changes in the DNA content of cells treated with nocodazole over time.…”

Section: Spc105 Bpm Does Not Enhance Sac Signalingsupporting

confidence: 87%

Minimization of a harmful cross-talk between mitotic checkpoint silencing and error correction

Verma

Sim

et al. 2018

Preprint

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Accurate chromosome segregation during cell division requires that the pair of sister kinetochores on each chromosome attach to microtubules originating from opposite spindle poles. This is ensured by the combined action of the Spindle Assembly Checkpoint (SAC), which detects unattached kinetochores, and an error correction mechanism that destabilizes incorrect attachment of both sister kinetochores to the same spindle pole. These processes are downregulated by Protein Phosphatase 1 (PP1), which both silences the SAC and stabilizes kinetochore-microtubule attachments. We find that this dual PP1 role can be problematic: if PP1 is recruited to the kinetochore for SAC silencing prior to chromosome biorientation, it interferes with error correction. We show that to mitigate this cross-talk, the yeast kinetochore uses independent PP1 sources to stabilize correct attachments and to silence the SAC, and also delays the recruitment of PP1 for SAC silencing. Consequently, chromosome biorientation precedes SAC silencing ensuring accurate chromosome segregation.

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Section: Spc105 Bpm Does Not Enhance Sac Signalingsupporting

confidence: 87%

Minimization of a harmful cross-talk between mitotic checkpoint silencing and error correction

Verma

Sim

et al. 2018

Preprint

Self Cite

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“…2). Colors of components correspond approximately to those in Figure 1; the red oval in the center symbolizes that tension can in principle affect the spindle-assembly checkpoint proteins, which associate (directly or indirectly) with Mps1-phosphorylated repeats on Spc105 (Aravamudhan et al 2016). …”

Section: Intercomplex Connectionsmentioning

confidence: 99%

Molecular Structures of Yeast Kinetochore Subcomplexes and Their Roles in Chromosome Segregation

Jenni

Dimitrova

Valverde

et al. 2017

Cold Spring Harb Symp Quant Biol

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Kinetochore molecular architecture exemplifies "form follows function." The simplifications that generated the one-chromosome:one-microtubule linkage in point-centromere yeast have enabled strategies for systematic structural analysis and highresolution visualization of many kinetochore components, leading to specific proposals for molecular mechanisms. We describe here some structural features that allow a kinetochore to remain attached to the end of a depolymerizing microtubule (MT) and some characteristics of the connections between substructures that permit very sensitive regulation by differential kinase activities. We emphasize in particular the importance of flexible connections between rod-like structural members and the integration of these members into a compliant cage-like assembly anchored on the MT by a sliding molecular ring.

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“…First, they must ensure that a single unattached kinetochore can produce a sufficiently large quantity of MCC so that anaphase is delayed and chromosome missegregation is averted. Second, they must also ensure that the generation of MCC does not scale linearly with the number of unattached kinetochores in the cell [93]. A dividing cell contains a large number of unattached kinetochores in prophase.…”

Section: Molecular Mechanisms Underlying Sac Activation and Inactimentioning

confidence: 99%

“…Since each MELT motif can bind one Bub3-Bub1 complex, 19 MELT motifs, in principle, should be able to bind 19 Bub3-Bub1 molecules, and generate a 19-fold higher SAC signal. However, careful analysis of Bub3 recruitment reveals that on average only 30% of the MELT motifs bind Bub3-Bub1 [93,122]. In fact, engineered KNL1 molecules with just a single MELT motif and the KI repeats suffice to activate the SAC when cells are treated with nocodazole [82].…”

Section: Directions For Future Investigations Of the Sacmentioning

confidence: 99%

A Cell Biological Perspective on Past, Present and Future Investigations of the Spindle Assembly Checkpoint

Joglekar¹

2016

Biology

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The spindle assembly checkpoint (SAC) is a quality control mechanism that ensures accurate chromosome segregation during cell division. It consists of a mechanochemical signal transduction mechanism that senses the attachment of chromosomes to the spindle, and a signaling cascade that inhibits cell division if one or more chromosomes are not attached. Extensive investigations of both these component systems of the SAC have synthesized a comprehensive understanding of the underlying molecular mechanisms. This review recounts the milestone results that elucidated the SAC, compiles a simple model of the complex molecular machinery underlying the SAC, and highlights poorly understood facets of the biochemical design and cell biological operation of the SAC that will drive research forward in the near future.

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Dual mechanisms regulate the recruitment of spindle assembly checkpoint proteins to the budding yeast kinetochore

Cited by 24 publications

References 49 publications

Minimization of a harmful cross-talk between mitotic checkpoint silencing and error correction

Minimization of a harmful cross-talk between mitotic checkpoint silencing and error correction

Molecular Structures of Yeast Kinetochore Subcomplexes and Their Roles in Chromosome Segregation

A Cell Biological Perspective on Past, Present and Future Investigations of the Spindle Assembly Checkpoint

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