Phosphoregulation of tropomyosin is crucial for actin cable turnover and division site placement.

Tropomyosin is a coiled-coil actin binding protein key to the stability of actin filaments. In muscle cells, tropomyosin is subject to calcium regulation, but its regulation in nonmuscle cells is not understood. Here, we provide evidence that the fission yeast tropomyosin, Cdc8, is regulated by phosphorylation of a serine residue.

Bub1 is not essential for the checkpoint response to unattached kinetochores in diploid human cells.

Error-free chromosome segregation during mitosis depends on a functional spindle assembly checkpoint (SAC). The SAC is a multi-component signalling system that is recruited to unattached or incorrectly attached kinetochores to catalyse the formation of a soluble inhibitor, known as the Mitotic Checkpoint Complex (MCC), which binds and inhibits the anaphase promoting complex (APC/C) [1]. We have previously proposed that two separable pathways, composed of KNL1-Bub3-Bub1 (KBB) and Rod-Zwilch-Zw10 (RZZ), recruit Mad1-Mad2 complexes to human kinetochores to activate the SAC [2].

Some assembly required: Redefining the mitotic checkpoint.

The spindle assembly checkpoint (also known as the spindle or mitotic checkpoint) is a surveillance system that ensures fidelity of chromosome segregation. Here we suggest, in light of historical and more recent evidence, that this signaling system monitors kinetochore attachment and spindle assembly by two distinct, but functionally overlapping, pathways.

Identification of a Sgo2-Dependent but Mad2-Independent Pathway Controlling Anaphase Onset in Fission Yeast.

The onset of anaphase is triggered by activation of the anaphase-promoting complex/cyclosome (APC/C) following silencing of the spindle assembly checkpoint (SAC). APC/C triggers ubiquitination of Securin and Cyclin B, which leads to loss of sister chromatid cohesion and inactivation of Cyclin B/Cdk1, respectively. This promotes relocalization of Aurora B kinase and other components of the chromosome passenger complex (CPC) from centromeres to the spindle midzone.

Bub3-Bub1 Binding to Spc7/KNL1 Toggles the Spindle Checkpoint Switch by Licensing the Interaction of Bub1 with Mad1-Mad2.

The spindle assembly checkpoint (SAC) ensures that sister chromatids do not separate until all chromosomes are attached to spindle microtubules and bi-oriented. Spindle checkpoint proteins, including Mad1, Mad2, Mad3 (BubR1), Bub1, Bub3, and Mph1 (Mps1), are recruited to unattached and/or tensionless kinetochores. SAC activation catalyzes the conversion of soluble Mad2 (O-Mad2) into a form (C-Mad2) that binds Cdc20, BubR1, and Bub3 to form the mitotic checkpoint complex (MCC), a potent inhibitor of the anaphase-promoting complex (APC/C).

Inferring orthologous gene regulatory networks using interspecies data fusion.

Motivation: The ability to jointly learn gene regulatory networks (GRNs) in, or leverage GRNs between related species would allow the vast amount of legacy data obtained in model organisms to inform the GRNs of more complex, or economically or medically relevant counterparts. Examples include transferring information from Arabidopsis thaliana into related crop species for food security purposes, or from mice into humans for medical applications. Here we develop two related Bayesian approaches to network inference that allow GRNs to be jointly inferred in, or leveraged between, several related species: in one framework, network information is directly propagated between species; in the second hierarchical approach, network information is propagated via an unobserved 'hypernetwork'.

Sharpening the anaphase switch.

The segregation of sister chromatids during mitosis is one of the most easily visualized, yet most remarkable, events during the life cycle of a cell. The accuracy of this process is essential to maintain ploidy during cell duplication. Over the past 20 years, substantial progress has been made in identifying components of both the kinetochore and the mitotic spindle that generate the force to move mitotic chromosomes.

Role and regulation of kinesin-8 motors through the cell cycle.

Members of the kinesin-8 motor family play a central role in controlling microtubule length throughout the eukaryotic cell cycle. Inactivation of kinesin-8 causes defects in cell polarity during interphase and astral and mitotic spindle length, metaphase chromosome alignment, timing of anaphase onset and accuracy of chromosome segregation. Although the biophysical mechanism by which kinesin-8 molecules influence microtubule dynamics has been studied extensively in a variety of species, a consensus view has yet to emerge.

The Rim15-endosulfine-PP2ACdc55 signalling module regulates entry into gametogenesis and quiescence via distinct mechanisms in budding yeast.

Quiescence and gametogenesis represent two distinct survival strategies in response to nutrient starvation in budding yeast. Precisely how environmental signals are sensed by yeast cells to trigger quiescence and gametogenesis is not fully understood. A conserved signalling module consisting of Greatwall kinase, Endosulfine and Protein Phosphatase PP2ACdc55 proteins regulates entry into mitosis in Xenopus egg extracts and meiotic maturation in flies.

Checkpoint proteins come under scrutiny.

Details are emerging of the interactions between the kinetochore and various spindle checkpoint proteins that ensure that sister chromatids are equally divided between daughter cells during cell division.

Monopolin subunit Csm1 associates with MIND complex to establish monopolar attachment of sister kinetochores at meiosis I.

Sexually reproducing organisms halve their cellular ploidy during gametogenesis by undergoing a specialized form of cell division known as meiosis. During meiosis, a single round of DNA replication is followed by two rounds of nuclear divisions (referred to as meiosis I and II). While sister kinetochores bind to microtubules emanating from opposite spindle poles during mitosis, they bind to microtubules originating from the same spindle pole during meiosis I.

Cell biology: polar expeditions for PP1.

A new study shows that phospho-dependent expulsion of type-1-phosphatase (PP1) from the spindle pole by Fin1 (NIMA) kinase ensures switch-like activation of Cyclin B-Cdk1 at the G2/M transition.

Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint.

The spindle assembly checkpoint (SAC) is the major surveillance system that ensures that sister chromatids do not separate until all chromosomes are correctly bioriented during mitosis. Components of the checkpoint include Mad1, Mad2, Mad3 (BubR1), Bub3, and the kinases Bub1, Mph1 (Mps1), and Aurora B. Checkpoint proteins are recruited to kinetochores when individual kinetochores are not bound to spindle microtubules or not under tension.

Plo1 phosphorylates Dam1 to promote chromosome bi-orientation in fission yeast.

The fungal-specific heterodecameric outer kinetochore DASH complex facilitates the interaction of kinetochores with spindle microtubules. In budding yeast, where kinetochores bind a single microtubule, the DASH complex is essential, and phosphorylation of Dam1 by the Aurora kinase homologue, Ipl1, causes detachment of kinetochores from spindle microtubules. We demonstrate that in the distantly related fission yeast, where the DASH complex is not essential for viability and kinetochores bind multiple microtubules, Dam1 is instead phosphorylated on serine 143 by the Polo kinase homologue, Plo1, during prometaphase and metaphase.

Nsk1 ensures accurate chromosome segregation by promoting association of kinetochores to spindle poles during anaphase B.

Type 1 phosphatase (PP1) antagonizes Aurora B kinase to stabilize kinetochore-microtubule attachments and to silence the spindle checkpoint. We screened for factors that exacerbate the growth defect of Δdis2 cells, which lack one of two catalytic subunits of PP1 in fission yeast, and identified Nsk1, a novel protein required for accurate chromosome segregation. During interphase, Nsk1 resides in the nucleolus but spreads throughout the nucleoplasm as cells enter mitosis.

Meiotic nuclear divisions in budding yeast require PP2A(Cdc55)-mediated antagonism of Net1 phosphorylation by Cdk.

During meiosis, one round of deoxyribonucleic acid replication is followed by two rounds of nuclear division. In Saccharomyces cerevisiae, activation of the Cdc14 early anaphase release (FEAR) network is required for exit from meiosis I but does not lead to the activation of origins of replication. The precise mechanism of how FEAR regulates meiosis is not understood.

Spindle checkpoint silencing requires association of PP1 to both Spc7 and kinesin-8 motors.

The spindle checkpoint is the prime cell-cycle control mechanism that ensures sister chromatids are bioriented before anaphase takes place. Aurora B kinase, the catalytic subunit of the chromosome passenger complex, both destabilizes kinetochore attachments that do not generate tension and simultaneously maintains the spindle checkpoint signal. However, it is unclear how the checkpoint is silenced following chromosome biorientation.

Ringing the changes: emerging roles for DASH at the kinetochore-microtubule Interface.

Regulated interaction between kinetochores and the mitotic spindle is essential for the fidelity of chromosome segregation. Potentially deleterious attachments are corrected during prometaphase and metaphase. Correct attachments must persist during anaphase, when spindle-generated forces separate chromosomes to opposite poles.

Two-component mediated peroxide sensing and signal transduction in fission yeast.

Two-component related proteins play a major role in regulating the oxidative stress response in the fission yeast, Schizosaccharomyces pombe. For example, the peroxide-sensing Mak2 and Mak3 histidine kinases regulate H(2)O(2)-induced activation of the Sty1 stress-activated protein kinase pathway, and the Skn7-related response regulator transcription factor, Prr1, is essential for activation of the core oxidative stress response genes. Here, we investigate the mechanism by which the S.

Bub3p facilitates spindle checkpoint silencing in fission yeast.

Although critical for spindle checkpoint signaling, the role kinetochores play in anaphase promoting complex (APC) inhibition remains unclear. Here we show that spindle checkpoint proteins are severely depleted from unattached kinetochores in fission yeast cells lacking Bub3p. Surprisingly, a robust mitotic arrest is maintained in the majority of bub3 Delta cells, yet they die, suggesting that Bub3p is essential for successful checkpoint recovery.

The Dam1/DASH complex is required for the retrieval of unclustered kinetochores in fission yeast.

In fission yeast centromeres cluster at the nuclear envelope in a region underlying the spindle pole body during interphase, an arrangement known as a Rabl configuration. We have identified a strain in which one pair of sister kinetochores is unclustered from the others and binds the nuclear envelope at a point distal to the spindle pole body. We show that during mitosis unclustered kinetochores are captured by intranuclear spindle microtubules which then pull the kinetochores back to one of the two spindle poles before they are bi-oriented on the mitotic spindle.

Sin1 binds to both ATF-2 and p38 and enhances ATF-2-dependent transcription in an SAPK signaling pathway.

Yeast Sin1 binds to the Sty1 kinase, a member of the stress-activated kinases (SAPKs), and is required for stress-induced phosphorylation and activation of the transcription factor Atf1, a homolog of the vertebrate-activating transcription factor-2 (ATF-2). Here we report that mammalian Sin1 plays an important role in the SAPK signaling pathway by binding to both ATF-2 and p38. In response to stress, ATF-2, a member of the ATF/cAMP response element-binding protein family, is phosphorylated by p38/Jun NH2-terminal protein kinase and activates the transcription of apoptosis-related genes.

Cdc25: mechanisms of checkpoint inhibition and recovery.

Members of the eukaryotic Cdc25 phosphatase family are key targets of the Chk1 and Chk2 checkpoint kinases, which inactivate Cdc25 to halt cell cycle progression when DNA is damaged or incompletely replicated. Now, new kinases that phosphorylate and inactivate Cdc25 are being discovered, including MAPKAP kinase-2, a component of the p38 stress-activated MAP kinase pathway. The roles of other kinases, such as cyclin-dependent kinase, Polo and Aurora A kinase, in controlling the localization or the activation of Cdc25, are controversial.

The DASH complex and Klp5/Klp6 kinesin coordinate bipolar chromosome attachment in fission yeast.

We identified a truncated allele of dam1 as a multicopy suppressor of the sensitivity of cdc13-117 (cyclin B) and mal3-1 (EB-1) cells to thiabendazole, a microtubule poison. We find that Dam1 binds to the plus end of spindle microtubules and kinetochores as cells enter mitosis and this is dependent on other components of the fission yeast DASH complex, including Ask1, Duo1, Spc34 and Dad1. By contrast, Dad1 remains bound to kinetochores throughout the cell cycle and its association is dependent on the Mis6 and Mal2, but not Mis12, Nuf2 or Cnp1, kinetochore proteins.