Mitotic CDKs control the metaphase–anaphase transition and trigger spindle elongation

Rahal, Rami; Amon, Angelika

doi:10.1101/gad.1638308

Cited by 57 publications

(88 citation statements)

References 73 publications

(116 reference statements)

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“…This work shows in addition, that mitotic cyclins are important for anaphase B progression as was recently be observed by Rahal and Amon. 6 However, this work suggests that defects in anaphase B progression and spindle elongation are not due to defects in microtubule elongation, as presumed, but instead to the formation of new bipolar spindle or bi-polar spindle re-forming. This, in addition, explains the apparently paradoxical results that Rahal and Amon point out, in which their clb1Δclb2VI fixed cells were mainly found in …”

Section: Methodsmentioning

confidence: 61%

“…Therefore, complementation by other mitotic cyclins was less efficient when G 2 /M checkpoint was activated. This could possibly be due to deregulated activity of the anaphase-promoting complex/cyclosome-Cdc20 that is regulated by mitotic cyclins 6,48,49 but also by DNA damage checkpoint [50][51][52][53][54][55] and reciprocally controls the stability/turnover of mitotic cyclins. 56 Interestingly, a role for Cdc20 in controlling spindle length and the stability of kinetochore microtubule in response to genotoxic stress has been suggested.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 The double mutants clb1Δclb2Δ and clb2Δclb3Δ also lead to arrest in G 2 /M with separated spindle pole bodies (SPBs) and short spindles, hence mitotic cyclins have been inferred to play a role in spindle elongation as well in budding yeast. 3,5,6 The identification of the roles of mitotic cyclins during anaphase in vivo has therefore been hindered by their essential functions in initiation of mitosis and by redundant activities. Consequently, the role of mitotic cyclins during progression through mitosis and, more particularly, during anaphase remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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New insights into the regulation of anaphase by mitotic cyclins in budding yeast

Signon¹

2011

Cell Cycle

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Section: Methodsmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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New insights into the regulation of anaphase by mitotic cyclins in budding yeast

Signon¹

2011

Cell Cycle

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“…Lower levels of Cdk1 activity are needed to induce the entry into mitosis than the metaphase-toanaphase transition, and Cdk1-Y19 phosphorylation functions at both these thresholds (Rahal and Amon 2008;. Our results suggest that at least three phosphatases regulate Cdk1 dephosphorylation and that the regulation of their activity may provide a mechanism for cells to activate pools of Cdk1 at different times and in different cellular locations.…”

Section: Discussionmentioning

confidence: 72%

Redundant Regulation of Cdk1 Tyrosine Dephosphorylation in Saccharomyces cerevisiae

et al. 2015

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Cdk1 activity drives both mitotic entry and the metaphase-to-anaphase transition in all eukaryotes. The kinase Wee1 and the phosphatase Cdc25 regulate the mitotic activity of Cdk1 by the reversible phosphorylation of a conserved tyrosine residue. Mutation of cdc25 in Schizosaccharomyces pombe blocks Cdk1 dephosphorylation and causes cell cycle arrest. In contrast, deletion of MIH1, the cdc25 homolog in Saccharomyces cerevisiae, is viable. Although Cdk1-Y19 phosphorylation is elevated during mitosis in mih1D cells, Cdk1 is dephosphorylated as cells progress into G 1 , suggesting that additional phosphatases regulate Cdk1 dephosphorylation. Here we show that the phosphatase Ptp1 also regulates Cdk1 dephosphorylation in vivo and can directly dephosphorylate Cdk1 in vitro. Using a novel in vivo phosphatase assay, we also show that PP2A bound to Rts1, the budding yeast B56-regulatory subunit, regulates dephosphorylation of Cdk1 independently of a function regulating Swe1, Mih1, or Ptp1, suggesting that PP2A Rts1 either directly dephosphorylates Cdk1-Y19 or regulates an unidentified phosphatase.KEYWORDS Cdc25/Mih1; Cdk1; PP2A; Wee1/Swe1; mitosis M ITOTIC onset is regulated in all eukaryotes by an increase in Cdk1 activity caused by the dephosphorylation of Cdk1 on a conserved inhibitory tyrosine (tyrosine 19 in budding yeast) (Nurse 1990). The Wee1 kinase phosphorylates and inhibits Cdk1 (Gould and Nurse 1989; Parker et al. 1992), and the Cdc25 phosphatase acts as a mitotic inducer by dephosphorylating and activating Cdk1 (Dunphy and Kumagai 1991;Gautier et al. 1991). wee1 mutants in fission yeast shorten G 2 by prematurely activating Cdk1 (Nurse 1975;Russell and Nurse 1987), whereas cdc25 mutants cannot accumulate sufficient Cdk1 activity to enter mitosis and arrest (Russell and Nurse 1986). Both Wee1 and Cdc25 are the targets of numerous cell-cycle checkpoints, all of which delay mitotic entry by activating Wee1 or inhibiting Cdc25 (Kellogg 2003). In budding yeast, Swe1 (the Wee1 homolog) and Mih1 (the Cdc25 homolog) also function prior to mitosis (Russell et al. 1989;Harvey and Kellogg 2003;Pal et al. 2008), but our recent work revealed that overexpression of Swe1 or activation of a Swe1-dependent checkpoint arrests cells in metaphase .Deletion of cdc25 in fission yeast is lethal and arrests cells in G 2 , indicating the essential role of Cdk1-Y15 dephosphorylation in fission yeast (Russell and Nurse 1986). In contrast, although deletion of MIH1 exhibits high Cdk1-Y19 phosphorylation during mitosis, these cells have only mild delays in mitotic entry and anaphase onset and initiate Cdk1-Y19 dephosphorylation at anaphase onset (Russell et al. 1989;Pal et al. 2008;. This behavior argues that at least one additional phosphatase functions redundantly with Mih1.Russell and colleagues (Millar et al. 1992) identified the fission yeast Pyp3 as a phosphatase that functions redundantly with Cdc25. Increased expression of pyp3 or the budding yeast and mammalian homologs PTP1, PTP1B and TC-PTP1, respectively, suppress...

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“…M-Cdk1 is also required to promote the full spindle elongation required for full anaphase. 29 We checked whether high Cln2-Cdk1 activity is able to activate APC Cdc20 by monitoring Pds1/Securin levels. 30 As shown in Figure 5B Pds1 levels remain stable in the presence of either Cln2(7A)-2xNLS alone or together with Cln2(7A) when CLB cyclin Cdk1 activity is inhibited.…”

Section: Cln2 Is Able To Promote S Phase Transcription But Not Mitosismentioning

confidence: 99%

G1 cyclin driven DNA replication

et al. 2015

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The mitotic cell cycle is driven by Cyclin-Dependent Kinases (CDK). CDK activation requires the binding of activatory subunits termed cyclins. Different waves of cyclins are expressed during the cell cycle, enabling CDKs to trigger phase specific events. For instance, S phase cyclins promote the initiation of DNA replication but not chromosome segregation. There are at least 2 explanations for how such regulation is achieved. According to one of the visions, cyclins confer intrinsic substrate specificity to the CDK catalytic subunit. Alternatively a quantitative model has been proposed, according to which ever-increasing CDK activity is required to trigger cell cycle events from G1 to M. If a quantitative control prevails, then an early cyclin should trigger later cycle events if accumulated at high enough levels at the right time and place. We show here that a G1 phase cyclin bears the potential to trigger DNA replication and promote S and G2 phase specific transcription.

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Mitotic CDKs control the metaphase–anaphase transition and trigger spindle elongation

Cited by 57 publications

References 73 publications

New insights into the regulation of anaphase by mitotic cyclins in budding yeast

New insights into the regulation of anaphase by mitotic cyclins in budding yeast

Redundant Regulation of Cdk1 Tyrosine Dephosphorylation in Saccharomyces cerevisiae

G1 cyclin driven DNA replication

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