scholarly journals Fission yeast ch-TOG/XMAP215 homologue Alp14 connects mitotic spindles with the kinetochore and is a component of the Mad2-dependent spindle checkpoint

2001 ◽  
Vol 20 (13) ◽  
pp. 3389-3401 ◽  
Author(s):  
M. A. Garcia
Keyword(s):  
Fission Yeast ◽  
Spindle Checkpoint ◽  
Mitotic Spindles

scholarly journals DNA Replication Checkpoint Control Mediated by the Spindle Checkpoint Protein Mad2p in Fission Yeast

2004 ◽  
Vol 279 (45) ◽  
pp. 47372-47378 ◽  
Author(s):  
Izumi Sugimoto ◽  
Hiroshi Murakami ◽  
Yuko Tonami ◽  
Akihiko Moriyama ◽  
Makoto Nakanishi
Keyword(s):  
Dna Replication ◽  
Fission Yeast ◽  
Spindle Checkpoint ◽  
Checkpoint Control ◽  
Replication Checkpoint ◽  
Checkpoint Protein ◽  
Dna Replication Checkpoint

scholarly journals The HECT E3 ligase Smurf2 is required for Mad2-dependent spindle assembly checkpoint

2008 ◽  
Vol 183 (2) ◽  
pp. 267-277 ◽  
Author(s):  
Evan C. Osmundson ◽  
Dipankar Ray ◽  
Finola E. Moore ◽  
Qingshen Gao ◽  
Gerald H. Thomsen ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Spindle Assembly Checkpoint ◽  
Spindle Checkpoint ◽  
E3 Ligase ◽  
Spindle Assembly ◽  
Cyclin B ◽  
Carboxyl Terminus ◽  
Anaphase Promoting Complex ◽  
Mitotic Spindles ◽  
Anaphase Onset

Activation of the anaphase-promoting complex/cyclosome (APC/C) by Cdc20 is critical for the metaphase–anaphase transition. APC/C-Cdc20 is required for polyubiquitination and degradation of securin and cyclin B at anaphase onset. The spindle assembly checkpoint delays APC/C-Cdc20 activation until all kinetochores attach to mitotic spindles. In this study, we demonstrate that a HECT (homologous to the E6-AP carboxyl terminus) ubiquitin ligase, Smurf2, is required for the spindle checkpoint. Smurf2 localizes to the centrosome, mitotic midbody, and centromeres. Smurf2 depletion or the expression of a catalytically inactive Smurf2 results in misaligned and lagging chromosomes, premature anaphase onset, and defective cytokinesis. Smurf2 inactivation prevents nocodazole-treated cells from accumulating cyclin B and securin and prometaphase arrest. The silencing of Cdc20 in Smurf2-depleted cells restores mitotic accumulation of cyclin B and securin. Smurf2 depletion results in enhanced polyubiquitination and degradation of Mad2, a critical checkpoint effector. Mad2 is mislocalized in Smurf2-depleted cells, suggesting that Smurf2 regulates the localization and stability of Mad2. These data indicate that Smurf2 is a novel mitotic regulator.

scholarly journals Interdependency of Fission Yeast Alp14/TOG and Coiled Coil Protein Alp7 in Microtubule Localization and Bipolar Spindle Formation

2004 ◽  
Vol 15 (4) ◽  
pp. 1609-1622 ◽  
Author(s):  
Masamitsu Sato ◽  
Leah Vardy ◽  
Miguel Angel Garcia ◽  
Nirada Koonrugsa ◽  
Takashi Toda
Keyword(s):  
Fission Yeast ◽  
Spindle Pole Body ◽  
Coiled Coil ◽  
Spindle Pole ◽  
Mitotic Spindles ◽  
Microtubule Organization ◽  
Spindle Formation ◽  
Bipolar Spindle ◽  
C Terminus ◽  
Step Model

The Dis1/TOG family plays a pivotal role in microtubule organization. In fission yeast, Alp14 and Dis1 share an essential function in bipolar spindle formation. Here, we characterize Alp7, a novel coiled-coil protein that is required for organization of bipolar spindles. Both Alp7 and Alp14 colocalize to the spindle pole body (SPB) and mitotic spindles. Alp14 localization to these sites is fully dependent upon Alp7. Conversely, in the absence of Alp14, Alp7 localizes to the SPBs, but not mitotic spindles. Alp7 forms a complex with Alp14, where the C-terminal region of Alp14 interacts with the coiled-coil domain of Alp7. Intriguingly, this Alp14 C terminus is necessary and sufficient for mitotic spindle localization. Overproduction of either full-length or coiled-coil region of Alp7 results in abnormal V-shaped spindles and stabilization of interphase microtubules, which is induced independent of Alp14. Alp7 may be a functional homologue of animal TACC. Our results shed light on an interdependent relationship between Alp14/TOG and Alp7. We propose a two-step model that accounts for the recruitment of Alp7 and Alp14 to the SPB and microtubules.

scholarly journals The Fission Yeast Crb2/Chk1 Pathway Coordinates the DNA Damage and Spindle Checkpoint in Response to Replication Stress Induced by Topoisomerase I Inhibitor

2005 ◽  
Vol 25 (17) ◽  
pp. 7889-7899 ◽  
Author(s):  
Ada Collura ◽  
Joel Blaisonneau ◽  
Giuseppe Baldacci ◽  
Stefania Francesconi
Keyword(s):  
Dna Damage ◽  
Fission Yeast ◽  
Topoisomerase I ◽  
Genome Stability ◽  
Cell Cycle Progression ◽  
Spindle Assembly Checkpoint ◽  
Genetic Material ◽  
Spindle Checkpoint ◽  
Dna Damage Checkpoint ◽  
Replicative Stress

ABSTRACT Living organisms experience constant threats that challenge their genome stability. The DNA damage checkpoint pathway coordinates cell cycle progression with DNA repair when DNA is damaged, thus ensuring faithful transmission of the genome. The spindle assembly checkpoint inhibits chromosome segregation until all chromosomes are properly attached to the spindle, ensuring accurate partition of the genetic material. Both the DNA damage and spindle checkpoint pathways participate in genome integrity. However, no clear connection between these two pathways has been described. Here, we analyze mutants in the BRCT domains of fission yeast Crb2, which mediates Chk1 activation, and provide evidence for a novel function of the Chk1 pathway. When the Crb2 mutants experience damaged replication forks upon inhibition of the religation activity of topoisomerase I, the Chk1 DNA damage pathway induces sustained activation of the spindle checkpoint, which in turn delays metaphase-to-anaphase transition in a Mad2-dependent fashion. This new pathway enhances cell survival and genome stability when cells undergo replicative stress in the absence of a proficient G2/M DNA damage checkpoint.

scholarly journals A Spindle Checkpoint Functions during Mitosis in the Early Caenorhabditis elegans Embryo

2005 ◽  
Vol 16 (3) ◽  
pp. 1056-1070 ◽  
Author(s):  
Sandra E. Encalada ◽  
John Willis ◽  
Rebecca Lyczak ◽  
Bruce Bowerman
Keyword(s):  
Caenorhabditis Elegans ◽  
Chromosome Segregation ◽  
Spindle Checkpoint ◽  
Metaphase Plate ◽  
Time Lapse ◽  
Cell Types ◽  
Embryonic Cells ◽  
Mitotic Spindles ◽  
Animal Cells ◽  
Dividing Cells

During mitosis, chromosome segregation is regulated by a spindle checkpoint mechanism. This checkpoint delays anaphase until all kinetochores are captured by microtubules from both spindle poles, chromosomes congress to the metaphase plate, and the tension between kinetochores and their attached microtubules is properly sensed. Although the spindle checkpoint can be activated in many different cell types, the role of this regulatory mechanism in rapidly dividing embryonic animal cells has remained controversial. Here, using time-lapse imaging of live embryonic cells, we show that chemical or mutational disruption of the mitotic spindle in early Caenorhabditis elegans embryos delays progression through mitosis. By reducing the function of conserved checkpoint genes in mutant embryos with defective mitotic spindles, we show that these delays require the spindle checkpoint. In the absence of a functional checkpoint, more severe defects in chromosome segregation are observed in mutants with abnormal mitotic spindles. We also show that the conserved kinesin CeMCAK, the CENP-F-related proteins HCP-1 and HCP-2, and the core kinetochore protein CeCENP-C all are required for this checkpoint. Our analysis indicates that spindle checkpoint mechanisms are functional in the rapidly dividing cells of an early animal embryo and that this checkpoint can prevent chromosome segregation defects during mitosis.

scholarly journals Shugoshin 2 Regulates Localization of the Chromosomal Passenger Proteins in Fission Yeast Mitosis

2007 ◽  
Vol 18 (5) ◽  
pp. 1657-1669 ◽  
Author(s):  
Vincent Vanoosthuyse ◽  
Sergey Prykhozhij ◽  
Kevin G. Hardwick
Keyword(s):  
Fission Yeast ◽  
Spindle Checkpoint ◽  
Aurora B ◽  
Checkpoint Activation ◽  
C Terminus ◽  
Chromosomal Passenger ◽  
Chromosomal Passenger Proteins ◽  
Passenger Proteins ◽  
Meiosis I ◽  
Mitotic Cells

Fission yeast has two members of the Shugoshin family, Sgo1 and Sgo2. Although Sgo1 has clearly been established as a protector of centromere cohesion in meiosis I, the roles of Sgo2 remain elusive. Here we show that Sgo2 is required to ensure proper chromosome biorientation upon recovery from a prolonged spindle checkpoint arrest. Consistent with this, Sgo2 is essential for maintaining the Passenger proteins on centromeres upon checkpoint activation. Interestingly, lack of Sgo2 has a more penetrant effect on the localization of Survivin than on the two other Passenger proteins INCENP and Aurora B, and the Survivin-INCENP complex but not the INCENP-Aurora B complex is destabilized in the absence of Sgo2. Finally we show that the conserved C-terminus of Sgo2 is crucial to maintain Sgo2 and Passenger proteins localization on centromeres upon prolonged checkpoint activation. Taken together, our results demonstrate that Sgo2 is important for chromosome biorientation and that it controls docking of the Passenger proteins on chromosomes in early mitotic cells.

scholarly journals Kinesin-8 effects on mitotic microtubule dynamics contribute to spindle function in fission yeast

2016 ◽  
Vol 27 (22) ◽  
pp. 3490-3514 ◽  
Author(s):  
Zachary R. Gergely ◽  
Ammon Crapo ◽  
Loren E. Hough ◽  
J. Richard McIntosh ◽  
Meredith D. Betterton
Keyword(s):  
Fission Yeast ◽  
Microtubule Dynamics ◽  
Chromosome Loss ◽  
Mitotic Spindles ◽  
Aberrant Chromosome ◽  
Large Fluctuations ◽  
Spindle Function ◽  
Chromosome Movements ◽  
Sliding Force

Kinesin-8 motor proteins destabilize microtubules. Their absence during cell division is associated with disorganized mitotic chromosome movements and chromosome loss. Despite recent work studying effects of kinesin-8s on microtubule dynamics, it remains unclear whether the kinesin-8 mitotic phenotypes are consequences of their effect on microtubule dynamics, their well-established motor activity, or additional, unknown functions. To better understand the role of kinesin-8 proteins in mitosis, we studied the effects of deletion of the fission yeast kinesin-8 proteins Klp5 and Klp6 on chromosome movements and spindle length dynamics. Aberrant microtubule-driven kinetochore pushing movements and tripolar mitotic spindles occurred in cells lacking Klp5 but not Klp6. Kinesin-8–deletion strains showed large fluctuations in metaphase spindle length, suggesting a disruption of spindle length stabilization. Comparison of our results from light microscopy with a mathematical model suggests that kinesin-8–induced effects on microtubule dynamics, kinetochore attachment stability, and sliding force in the spindle can explain the aberrant chromosome movements and spindle length fluctuations seen.

scholarly journals Mal3, the fission yeast EB1 homologue, cooperates with Bub1 spindle checkpoint to prevent monopolar attachment

EMBO Reports ◽  
2005 ◽  
Vol 6 (12) ◽  
pp. 1194-1200 ◽  
Author(s):  
Kazuhide Asakawa ◽  
Mika Toya ◽  
Masamitsu Sato ◽  
Muneyoshi Kanai ◽  
Kazunori Kume ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Spindle Checkpoint

scholarly journals Kinetochore Targeting of Fission Yeast Mad and Bub Proteins Is Essential for Spindle Checkpoint Function but Not for All Chromosome Segregation Roles of Bub1p

2004 ◽  
Vol 24 (22) ◽  
pp. 9786-9801 ◽  
Author(s):  
Vincent Vanoosthuyse ◽  
Rebekka Valsdottir ◽  
Jean-Paul Javerzat ◽  
Kevin G. Hardwick
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Chromosome Segregation ◽  
Chromatin Immunoprecipitation ◽  
Spindle Checkpoint ◽  
Central Domain ◽  
Checkpoint Response ◽  
Terminal Domain ◽  
Microtubule Attachment ◽  
Lines Of Evidence

ABSTRACT Several lines of evidence suggest that kinetochores are organizing centers for the spindle checkpoint response and the synthesis of a “wait anaphase” signal in cases of incomplete or improper kinetochore-microtubule attachment. Here we characterize Schizosaccharomyces pombe Bub3p and study the recruitment of spindle checkpoint components to kinetochores. We demonstrate by chromatin immunoprecipitation that they all interact with the central domain of centromeres, consistent with their role in monitoring kinetochore-microtubule interactions. Bub1p and Bub3p are dependent upon one another, but independent of the Mad proteins, for their kinetochore localization. We demonstrate a clear role for the highly conserved N-terminal domain of Bub1p in the robust targeting of Bub1p, Bub3p, and Mad3p to kinetochores and show that this is crucial for an efficient checkpoint response. Surprisingly, neither this domain nor kinetochore localization is required for other functions of Bub1p in chromosome segregation.

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