Mitotic Exit in the Absence of Separase Activity

doi:10.1091/MBC.E08-10-1042

Home
/
Papers
/
Mitotic Exit in the Absence of Separase Activity

Journal Article•DOI•

Mitotic Exit in the Absence of Separase Activity

Ying Lu¹, Frederick R. Cross¹•Institutions (1)

Rockefeller University¹

01 Mar 2009-Molecular Biology of the Cell (American Society for Cell Biology)-Vol. 20, Iss: 5, pp 1576-1591

TL;DR: The first quantitative measure for Cdc14 release based on colocalization with the Net1 nucleolar anchor is defined, indicating efficient CDC14 release upon MEN activation; release driven by Esp1 in the absence of microtubules was inefficient and incapable of driving ME.

read less

Abstract: In budding yeast, three interdigitated pathways regulate mitotic exit (ME): mitotic cyclin–cyclin-dependent kinase (Cdk) inactivation; the Cdc14 early anaphase release (FEAR) network, including a n...

...read moreread less

Content maybe subject to copyright Report

Citations

PDF

Open Access

More filters

Journal Article•DOI•

Systems-level feedback in cell-cycle control

[...]

Bela Novak¹, P. K. Vinod¹, Paula Freire¹, Orsolya Kapuy¹•Institutions (1)

University of Oxford¹

01 Oct 2010-Biochemical Society Transactions

TL;DR: Despite variations in the molecular details of the oscillatory mechanism, the underlying network motifs responsible for the oscillations are always well-conserved and driven by a negative-feedback loop amplified by double-negative feedbacks.

...read moreread less

Abstract: Alternation of chromosome replication and segregation is essential for successful completion of the cell cycle and it requires an oscillation of Cdk1 (cyclin-dependent kinase 1)–CycB (cyclin B) activity. In the present review, we illustrate the essential features of checkpoint controlled and uncontrolled cell-cycle oscillations by using mechanical metaphors. Despite variations in the molecular details of the oscillatory mechanism, the underlying network motifs responsible for the oscillations are always well-conserved. The checkpoint-controlled cell cycles are always driven by a negative-feedback loop amplified by double-negative feedbacks (antagonism).

...read moreread less

16 citations

Journal Article•DOI•

A Role for the Budding Yeast Separase, Esp1, in Ty1 Element Retrotransposition

[...]

Krystina Ho¹, Lina Ma¹, Stephanie Cheung¹, Savrina Manhas¹, Nancy N. Fang¹, Kaiqian Wang¹, Barry P. Young¹, Christopher J. R. Loewen¹, Thibault Mayor¹, Vivien Measday¹ - Show less +6 more•Institutions (1)

University of British Columbia¹

30 Mar 2015-PLOS Genetics

TL;DR: It is proposed that Esp1 serves two roles to mediate Ty1 transposition – one to remove cohesin and the second to target Ty1-IN to chromatin.

...read moreread less

Abstract: Separase/Esp1 is a protease required at the onset of anaphase to cleave cohesin and thereby enable sister chromatid separation. Esp1 also promotes release of the Cdc14 phosphatase from the nucleolus to enable mitotic exit. To uncover other potential roles for separase, we performed two complementary genome-wide genetic interaction screens with a strain carrying the budding yeast esp1-1 separase mutation. We identified 161 genes that when mutated aggravate esp1-1 growth and 44 genes that upon increased dosage are detrimental to esp1-1 viability. In addition to the expected cell cycle and sister chromatid segregation genes that were identified, 24% of the genes identified in the esp1-1 genetic screens have a role in Ty1 element retrotransposition. Retrotransposons, like retroviruses, replicate through reverse transcription of an mRNA intermediate and the resultant cDNA product is integrated into the genome by a conserved transposon or retrovirus encoded integrase protein. We purified Esp1 from yeast and identified an interaction between Esp1 and Ty1 integrase using mass spectrometry that was subsequently confirmed by co-immunoprecipitation analysis. Ty1 transposon mobility and insertion upstream of the SUF16 tRNA gene are both reduced in an esp1-1 strain but increased in cohesin mutant strains. Securin/Pds1, which is required for efficient localization of Esp1 to the nucleus, is also required for efficient Ty1 transposition. We propose that Esp1 serves two roles to mediate Ty1 transposition - one to remove cohesin and the second to target Ty1-IN to chromatin.

...read moreread less

16 citations

Cites background from "Mitotic Exit in the Absence of Sepa..."

...Cleavage of cohesin by separase is important for triggering the end of the cell cycle [65]....
[...]

Journal Article•DOI•

A mathematical model of mitotic exit in budding yeast: the role of Polo kinase.

[...]

Baris Hancioglu¹, John J. Tyson¹•Institutions (1)

Virginia Tech¹

23 Feb 2012-PLOS ONE

TL;DR: A mathematical model is proposed for the molecular events during mitotic exit in budding yeast and clarifies the roles of Polo-like kinase (Cdc5) in the Cdc14 early anaphase release pathway and in the G-protein regulated mitoticexit network.

...read moreread less

Abstract: Cell cycle progression in eukaryotes is regulated by periodic activation and inactivation of a family of cyclin-dependent kinases (Cdk's). Entry into mitosis requires phosphorylation of many proteins targeted by mitotic Cdk, and exit from mitosis requires proteolysis of mitotic cyclins and dephosphorylation of their targeted proteins. Mitotic exit in budding yeast is known to involve the interplay of mitotic kinases (Cdk and Polo kinases) and phosphatases (Cdc55/PP2A and Cdc14), as well as the action of the anaphase promoting complex (APC) in degrading specific proteins in anaphase and telophase. To understand the intricacies of this mechanism, we propose a mathematical model for the molecular events during mitotic exit in budding yeast. The model captures the dynamics of this network in wild-type yeast cells and 110 mutant strains. The model clarifies the roles of Polo-like kinase (Cdc5) in the Cdc14 early anaphase release pathway and in the G-protein regulated mitotic exit network.

...read moreread less

15 citations

Cites background from "Mitotic Exit in the Absence of Sepa..."

...Cdc5 is dispensable when MEN is hyperactivated by overexpression of a truncated version of Cdc15 (see Figure 4D), which may explain the phenotype of the met-cdc5-repress GALCDC15[1-750] mutant strain [30]....
[...]
...Both proteolytic and nonproteolytic activity of Esp1 contributes to ME Overexpressed separase is sufficient to trigger Cdc14 release (simulated in Figure 9A) in cells arrested in metaphase by depletion of Cdc20 [17,56,57]....
[...]
...Our model incorporates both proteolytic and nonproteolytic functions of Esp1; nonproteolytic function of Esp1 leads to FEAR activation [17,56], and its proteolytic activity is necessary for spindle elongation and MEN activation [57]....
[...]

Journal Article•DOI•

A role for GPN-loop GTPase yGPN1 in sister chromatid cohesion.

[...]

Béatrice Alonso, Guylaine Chaussinand, Jean Armengaud, Christian Godon¹•Institutions (1)

Commissariat à l'énergie atomique et aux énergies alternatives¹

01 Jun 2011-Cell Cycle

TL;DR: It is shown that the conserved and essential GPN loop GTPase yGPN1 in Saccharomyces cerevisiae is involved in sister chromatid cohesion mechanisms and the sharp slowdown in progression of the S phase observed in cells where yGpn1 expression is down-regulated strongly suggests that yGPGPN1 is necessary for DNA replication.

...read moreread less

Abstract: Sister chromatid cohesion and separation, involving the cohesin complex, are crucial for accurate inheritance of genetic information. This complex is also fundamental for efficient post-replicative repair of DNA double-strand breaks and has a key role in the mechanisms of gene transcription control. Cohesin is subjected to many post-translational modifications but the regulators implicated in the control of its activity have been poorly described. Here, we show that the conserved and essential GPN loop GTPase yGPN1 in Saccharomyces cerevisiae is involved in sister chromatid cohesion mechanisms. Based on a sister chromatid cohesion assay, we found that over-expression of the yGPN1 gene promotes sister chromatid separation during anaphase. The sharp slowdown in progression of the S phase observed in cells where yGPN1 expression is down-regulated strongly suggests that yGPN1 is necessary for DNA replication. Moreover, analysis of yGPN1 protein-protein interaction network highlights the yGPN1 links with DNA replication, sister chromatid cohesion/separation and the gene expression process.

...read moreread less

13 citations

Dissertation•

Inhibition of Cdc42 during mitotic exit is required for cytokinesis in Saccharomyces cerevisiae

[...]

Benjamin David Atkins

25 Feb 2014

TL;DR: In this paper, a decrease in Cdc42 activation during mitotic exit is necessary to allow localization of key cytokinesis regulators and proper septum formation, which is called septus formation.

...read moreread less

Abstract: A decrease in Cdc42 activation during mitotic exit is necessary to allow localization of key cytokinesis regulators and proper septum formation.

...read moreread less

12 citations

1
…
2
3
4
5
6
7
8
…
9

Collapse

References

PDF

Open Access

More filters

Journal Article•DOI•

Comprehensive Identification of Cell Cycle–regulated Genes of the Yeast Saccharomyces cerevisiae by Microarray Hybridization

[...]

Paul T. Spellman¹, Gavin Sherlock², Gavin Sherlock¹, Michael Q. Zhang², Vishwanath R. Iyer¹, Kirk R. Anders¹, Michael B. Eisen¹, Patrick O. Brown³, Patrick O. Brown¹, David Botstein¹, Bruce Futcher² - Show less +7 more•Institutions (3)

Stanford University¹, Cold Spring Harbor Laboratory², Howard Hughes Medical Institute³

01 Dec 1998-Molecular Biology of the Cell

TL;DR: A comprehensive catalog of yeast genes whose transcript levels vary periodically within the cell cycle is created, and it is found that the mRNA levels of more than half of these 800 genes respond to one or both of these cyclins.

...read moreread less

Abstract: We sought to create a comprehensive catalog of yeast genes whose transcript levels vary periodically within the cell cycle. To this end, we used DNA microarrays and samples from yeast cultures sync...

...read moreread less

5,176 citations

"Mitotic Exit in the Absence of Sepa..." refers background in this paper

...We confirmed that Pds1 was not degraded despite expression of GAL-SIC1-4A (in fact, its level increased [Supplemental Figure 1C], perhaps due to increased transcription after mitosis [Spellman et al., 1998])....
[...]
...developed by Sullivan and Uhlmann (2003). Cells were depleted of Cdc20 and arrested in metaphase, by using a methionine-suppressible MET3-CDC20 construct (Sullivan and Uhlmann, 2003)....
[...]

Journal Article•DOI•

Cohesins: chromosomal proteins that prevent premature separation of sister chromatids

[...]

Christine Michaelis¹, Rafal Ciosk¹, Kim Nasmyth¹•Institutions (1)

Research Institute of Molecular Pathology¹

03 Oct 1997-Cell

TL;DR: Three chromosmal proteins that prevent premature separation of sister chromatids in yeast are described, two of which are members of the SMC family, which are putative ATPases with coiled-coil domains.

...read moreread less

1,545 citations

"Mitotic Exit in the Absence of Sepa..." refers background in this paper

...The temperature-sensitive scc1-73 cohesin allele (Michaelis et al., 1997) allows sister chromatid separation without Esp1 activity at restrictive temperature (Uhlmann et al....
[...]
...The temperature-sensitive scc1-73 cohesin allele (Michaelis et al., 1997) allows sister chromatid separation without Esp1 activity at restrictive temperature (Uhlmann et al., 1999)....
[...]

Journal Article•DOI•

Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1

[...]

Frank Uhlmann¹, Friedrich Lottspeich², Kim Nasmyth¹•Institutions (2)

Research Institute of Molecular Pathology¹, Max Planck Society²

01 Jul 1999-Nature

TL;DR: It is shown that Esp1 causes the dissociation of Scc1 from chromosomes by stimulating its cleavage by proteolysis, and a mutant SCC1 is described that is resistant to Esp1-dependent cleavage and which blocks both sister-chromatid separation and the dissociations from chromosomes.

...read moreread less

Abstract: Cohesion between sister chromatids is established during DNA replication and depends on a multiprotein complex called cohesin Attachment of sister kinetochores to the mitotic spindle during mitosis generates forces that would immediately split sister chromatids were it not opposed by cohesion Cohesion is essential for the alignment of chromosomes in metaphase but must be abolished for sister separation to start during anaphase In the budding yeast Saccharomyces cerevisiae, loss of sister-chromatid cohesion depends on a separating protein (separin) called Esp1 and is accompanied by dissociation from the chromosomes of the cohesion subunit Scc1 Here we show that Esp1 causes the dissociation of Scc1 from chromosomes by stimulating its cleavage by proteolysis A mutant Scc1 is described that is resistant to Esp1-dependent cleavage and which blocks both sister-chromatid separation and the dissociation of Scc1 from chromosomes The evolutionary conservation of separins indicates that the proteolytic cleavage of cohesion proteins might be a general mechanism for triggering anaphase

...read moreread less

1,021 citations

"Mitotic Exit in the Absence of Sepa..." refers background in this paper

...The temperature-sensitive scc1-73 cohesin allele (Michaelis et al., 1997) allows sister chromatid separation without Esp1 activity at restrictive temperature (Uhlmann et al., 1999)....
[...]
...At 37°C, 35% initially unbudded cells elongated the spindle in spite of galactose addition, suggesting inefficient expression of GAL1-SCC1-RRDD at 37°C....
[...]
...A MYO1-GFP TUB1-GFP strain lacking GAL1-SCC1-RRDD (BD78-2C) was treated in parallel as a control, pooling bud-to-bud data for mothers and daughters....
[...]
...In these experiments, blocking sister chromatid separation does not block Esp1 activation, because endogenous Scc1 is cleaved on schedule even in the presence of ectopic Scc1RRDD (Uhlmann et al., 1999)....
[...]
...This question has been examined previously with the use of the noncleavable version of Scc1 expressed from the GAL1 promoter (GAL1-SCC1-RRDD) (Uhlmann et al., 1999)....
[...]

Journal Article•DOI•

Regulatable promoters of Saccharomyces cerevisiae: comparison of transcriptional activity and their use for heterologous expression

[...]

Dominik Mumberg¹, Rolf Müller, Martin Funk•Institutions (1)

University of Marburg¹

01 Jan 1994-Nucleic Acids Research

1,011 citations

"Mitotic Exit in the Absence of Sepa..." refers background in this paper

...The potential lethality of this allele was overcome by mildly overexpressing Esp1 under a truncated GAL1 promoter (Mumberg et al., 1994), GALS-ESP1....
[...]

Journal Article•DOI•

The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae

[...]

Etienne Schwob¹, Thomas Böhm¹, Michael D. Mendenhall², Kim Nasmyth¹•Institutions (2)

Research Institute of Molecular Pathology¹, University of Kentucky²

21 Oct 1994-Cell

TL;DR: It is shown that DNA replication also requires activation of Cdc28 by B-type (Clb) cyclins, and proteolysis of a cyclin-specific inhibitor of CDC28 is an essential aspect of the G1 to S phase transition.

...read moreread less

951 citations

"Mitotic Exit in the Absence of Sepa..." refers background in this paper

...DNA replication in the next cell cycle did not occur, presumably because of stable Sic1 accumulation ( Schwob et al., 1994; Verma et al., 1997)....
[...]
...DNA replication in the next cell cycle did not occur, presumably because of stable Sic1 accumulation (Schwob et al., 1994; Verma et al., 1997)....
[...]