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Spindle checkpoint silencing: ensuring rapid and concerted anaphase onset.

Hardwick KG, Shah JV - F1000 Biol Rep (2010)

Bottom Line: Such delays can last for just a few minutes or several hours, but very shortly after all chromosomes achieve bi-orientation, a remarkably synchronous anaphase ensues.We are beginning to understand the pathways involved in silencing spindle checkpoint signals and subsequent activation of the anaphase-promoting complex.Here, we review recent advances made in our understanding of the molecular mechanisms regulating this critical cell cycle transition.

View Article: PubMed Central - PubMed

ABSTRACT
The spindle checkpoint delays anaphase onset in the presence of defective kinetochore-microtubule attachments. Such delays can last for just a few minutes or several hours, but very shortly after all chromosomes achieve bi-orientation, a remarkably synchronous anaphase ensues. We are beginning to understand the pathways involved in silencing spindle checkpoint signals and subsequent activation of the anaphase-promoting complex. Here, we review recent advances made in our understanding of the molecular mechanisms regulating this critical cell cycle transition.

No MeSH data available.


Related in: MedlinePlus

Silencing of the checkpoint acts both in the cytoplasm (a) and locally at each kinetochore (b) upon microtubule attachment.At a single kinetochore, the binding of the microtubule and subsequent recruitment and activation of protein phosphatase 1 (PP1) locally reduce checkpoint kinase activity and release checkpoint complexes via dissociation of Mad1/Mad2 or translocation along microtubules via dynein. Loss of the single generators culminates in the total loss of generation when all chromosomes become attached. The remaining cytoplasmic inhibitory complexes (MCC-APC/C) are dissociated in part by the natural decay in the absence of generation and also by the activation of pathways that enhance dissociation to produce the synchronous onset of anaphase. The dissociation activity results in the activation of the APC/C by Cdc20, the ubiquitination and degradation of cyclin B and securin, and the onset of anaphase. APC/C, anaphase-promoting complex/cyclosome; AurB, Aurora B kinase; KNL1, kinetochore- 1; Mad, mitotic arrest defective; MCC, mitotic checkpoint complex; Mps1, monopolar spindle 1; RZZ, rough deal, zeste white 10, zwilch.
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fig-002: Silencing of the checkpoint acts both in the cytoplasm (a) and locally at each kinetochore (b) upon microtubule attachment.At a single kinetochore, the binding of the microtubule and subsequent recruitment and activation of protein phosphatase 1 (PP1) locally reduce checkpoint kinase activity and release checkpoint complexes via dissociation of Mad1/Mad2 or translocation along microtubules via dynein. Loss of the single generators culminates in the total loss of generation when all chromosomes become attached. The remaining cytoplasmic inhibitory complexes (MCC-APC/C) are dissociated in part by the natural decay in the absence of generation and also by the activation of pathways that enhance dissociation to produce the synchronous onset of anaphase. The dissociation activity results in the activation of the APC/C by Cdc20, the ubiquitination and degradation of cyclin B and securin, and the onset of anaphase. APC/C, anaphase-promoting complex/cyclosome; AurB, Aurora B kinase; KNL1, kinetochore- 1; Mad, mitotic arrest defective; MCC, mitotic checkpoint complex; Mps1, monopolar spindle 1; RZZ, rough deal, zeste white 10, zwilch.

Mentions: Once such attachments are achieved, several kinetochore-based factors act coordinately to stop kinetochore-mediated Mad2-Cdc20 complex generation (see below and Figure 2). However, preventing Mad2-Cdc20 production at kinetochores is not sufficient and the existing inhibitors in the cytoplasm and any cytoplasmic amplification mechanisms must be rapidly quenched to ensure a timely and synchronous anaphase [4,5].


Spindle checkpoint silencing: ensuring rapid and concerted anaphase onset.

Hardwick KG, Shah JV - F1000 Biol Rep (2010)

Silencing of the checkpoint acts both in the cytoplasm (a) and locally at each kinetochore (b) upon microtubule attachment.At a single kinetochore, the binding of the microtubule and subsequent recruitment and activation of protein phosphatase 1 (PP1) locally reduce checkpoint kinase activity and release checkpoint complexes via dissociation of Mad1/Mad2 or translocation along microtubules via dynein. Loss of the single generators culminates in the total loss of generation when all chromosomes become attached. The remaining cytoplasmic inhibitory complexes (MCC-APC/C) are dissociated in part by the natural decay in the absence of generation and also by the activation of pathways that enhance dissociation to produce the synchronous onset of anaphase. The dissociation activity results in the activation of the APC/C by Cdc20, the ubiquitination and degradation of cyclin B and securin, and the onset of anaphase. APC/C, anaphase-promoting complex/cyclosome; AurB, Aurora B kinase; KNL1, kinetochore- 1; Mad, mitotic arrest defective; MCC, mitotic checkpoint complex; Mps1, monopolar spindle 1; RZZ, rough deal, zeste white 10, zwilch.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2990540&req=5

fig-002: Silencing of the checkpoint acts both in the cytoplasm (a) and locally at each kinetochore (b) upon microtubule attachment.At a single kinetochore, the binding of the microtubule and subsequent recruitment and activation of protein phosphatase 1 (PP1) locally reduce checkpoint kinase activity and release checkpoint complexes via dissociation of Mad1/Mad2 or translocation along microtubules via dynein. Loss of the single generators culminates in the total loss of generation when all chromosomes become attached. The remaining cytoplasmic inhibitory complexes (MCC-APC/C) are dissociated in part by the natural decay in the absence of generation and also by the activation of pathways that enhance dissociation to produce the synchronous onset of anaphase. The dissociation activity results in the activation of the APC/C by Cdc20, the ubiquitination and degradation of cyclin B and securin, and the onset of anaphase. APC/C, anaphase-promoting complex/cyclosome; AurB, Aurora B kinase; KNL1, kinetochore- 1; Mad, mitotic arrest defective; MCC, mitotic checkpoint complex; Mps1, monopolar spindle 1; RZZ, rough deal, zeste white 10, zwilch.
Mentions: Once such attachments are achieved, several kinetochore-based factors act coordinately to stop kinetochore-mediated Mad2-Cdc20 complex generation (see below and Figure 2). However, preventing Mad2-Cdc20 production at kinetochores is not sufficient and the existing inhibitors in the cytoplasm and any cytoplasmic amplification mechanisms must be rapidly quenched to ensure a timely and synchronous anaphase [4,5].

Bottom Line: Such delays can last for just a few minutes or several hours, but very shortly after all chromosomes achieve bi-orientation, a remarkably synchronous anaphase ensues.We are beginning to understand the pathways involved in silencing spindle checkpoint signals and subsequent activation of the anaphase-promoting complex.Here, we review recent advances made in our understanding of the molecular mechanisms regulating this critical cell cycle transition.

View Article: PubMed Central - PubMed

ABSTRACT
The spindle checkpoint delays anaphase onset in the presence of defective kinetochore-microtubule attachments. Such delays can last for just a few minutes or several hours, but very shortly after all chromosomes achieve bi-orientation, a remarkably synchronous anaphase ensues. We are beginning to understand the pathways involved in silencing spindle checkpoint signals and subsequent activation of the anaphase-promoting complex. Here, we review recent advances made in our understanding of the molecular mechanisms regulating this critical cell cycle transition.

No MeSH data available.


Related in: MedlinePlus