The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond

During mitosis, correct bipolar chromosome attachment to the mitotic spindle is an essential prerequisite for the equal segregation of chromosomes. The spindle assembly checkpoint can prevent chromosome segregation as long as not all chromosome pairs have obtained bipolar attachment to the spindle. The chromosomal passenger complex plays a crucial role during chromosome alignment by correcting faulty chromosome-spindle interactions (e.g. attachments that do not generate tension). In the process of doing so, the chromosomal passenger complex generates unattached chromosomes, a specific situation that is known to promote checkpoint activity. However, several studies have implicated an additional, more direct role for the chromosomal passenger complex in enforcing the mitotic arrest imposed by the spindle assembly checkpoint. In this review, we discuss the different roles played by the chromosomal passenger complex in ensuring proper mitotic checkpoint function. Additionally, we discuss the possibility that besides monitoring the presence of unattached kinetochores, the spindle assembly checkpoint may also be capable of responding to chromosome-microtubule interactions that do not generate tension and we propose experimental set-ups to study this

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond-1

obtain bipolar spindle attachments, improper attachments (syntelic – depicted here-, and merotelic attachments) need to be corrected to prevent chromosome segregation errors. Aurora B in complex with its fellow passenger proteins is necessary for this correction process. Through the phosphorylation of kinetochore proteins that bind microtubules it modifies the stability or affinity of the kinetochore-microtubule interaction. As a consequence microtubules detach from the kinetochore allowing new rounds of attachments until bipolarity is obtained. However, during this correction process unattached are created capable of inhibiting the APC/C [33]. As such Aurora B's role in checkpoint function can be considered an indirect consequence of its microtubule destabilising activity.<p><b>Copyright information:</b></p><p>Taken from "The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond"</p><p>http://www.celldiv.com/content/3/1/10</p><p>Cell Division 2008;3():10-10.</p><p>Published online 28 May 2008</p><p>PMCID:PMC2430558.</p><p></p

The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond-2

S, the chromosomal passenger complex not only destabilises these attachments but also elicits an additional signal that inhibits the APC/C [35]. This could be via direct phosphorylation of APC/C subunits, or via direct control of the spindle assembly checkpoint. Ways be which the chromosomal passenger complex could exert direct control over the spindle checkpoint are through regulation of BubR1/Bub1 kinetochore levels, modulation of the mitotic checkpoint complex or via an as yet unknown pathway. Regardless the mechanism, this additional signal is thought to amplify the unattached kinetochore-derived signal, resulting in a robust checkpoint response when the number of unattached kinetochores is low.<p><b>Copyright information:</b></p><p>Taken from "The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond"</p><p>http://www.celldiv.com/content/3/1/10</p><p>Cell Division 2008;3():10-10.</p><p>Published online 28 May 2008</p><p>PMCID:PMC2430558.</p><p></p

The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond-3

Ever, even when all kinetochores are unattached the spindle assembly checkpoint is not capable of inhibiting all APC/C's which might explain why these cells do eventually exit from mitosis (mitotic slippage) [58]. If Aurora B is inactivated in these cells, less APC/C's will be inhibited. Still this is sufficient to allow a mitotic delay, but this delay is significantly shorter than when Aurora B is active [14, 15]. (B) Treatment with the microtubule stabilising agent paclitaxel induces a mitotic arrest with a few unattached kinetochores [35] most likely inhibiting less APC/C's than when all kinetochores are unattached. Yet, this number of inhibited APC/C's is sufficient to sustain a robust checkpoint-dependent arrest. Since the unattached kinetochores are generated under the influence of the chromosomal passenger complex/Aurora B [35], inhibition of Aurora B will now silence both the unattached kinetochore-derived checkpoint signal and the additional amplification signal, resulting in an override of the spindle assembly checkpoint. (C) Expression of a chromosomal passenger complex that lacks the coiled-coil domain of INCENP does not affect the microtubule destabilising activity of Aurora B. In the presence of paclitaxel unattached kinetochores are therefore generated but this does not result in a checkpoint-dependent arrest [35]. We propose that due to the low number of unattached kinetochores that are now inhibiting the APC/C, the spindle checkpoint becomes more dependent on this additional chromosomal passenger complex-generated amplification signal to inhibit a sufficient number of APC/C's that allow a robust mitotic arrest.<p><b>Copyright information:</b></p><p>Taken from "The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond"</p><p>http://www.celldiv.com/content/3/1/10</p><p>Cell Division 2008;3():10-10.</p><p>Published online 28 May 2008</p><p>PMCID:PMC2430558.</p><p></p

The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond-0

NP (which results in knock-down of all chromosomal passenger complex components). Transfected cells were released from a 24 h thymidine block into the indicated drugs. Eighteen hours after the release cells were fixed and prepared for FACS analysis. The MPM2 antibody was used to determine the mitotic index. This type of experiment shows that knock-down of a classical checkpoint protein (Mad2) does not allow cells to accumulate in mitosis with any of the drugs, while knock-down of the chromosomal passenger complex affects the response to paclitaxel and monastrol more dramatically than the response to nocodazole.<p><b>Copyright information:</b></p><p>Taken from "The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond"</p><p>http://www.celldiv.com/content/3/1/10</p><p>Cell Division 2008;3():10-10.</p><p>Published online 28 May 2008</p><p>PMCID:PMC2430558.</p><p></p

Mechanistic basis for Sgo1-mediated centromere localization and function of the CPC.

Centromere association of the chromosomal passenger complex (CPC; Borealin-Survivin-INCENP-Aurora B) and Sgo1 is crucial for chromosome biorientation, a process essential for error-free chromosome segregation. Phosphorylated histone H3 Thr3 (H3T3ph; directly recognized by Survivin) and histone H2A Thr120 (H2AT120ph; indirectly recognized via Sgo1), together with CPC's intrinsic nucleosome-binding ability, facilitate CPC centromere recruitment. However, the molecular basis for CPC-Sgo1 binding and how their physical interaction influences CPC centromere localization are lacking. Here, using an integrative structure-function approach, we show that the "histone H3-like" Sgo1 N-terminal tail-Survivin BIR domain interaction acts as a hotspot essential for CPC-Sgo1 assembly, while downstream Sgo1 residues and Borealin contribute for high-affinity binding. Disrupting Sgo1-Survivin interaction abolished CPC-Sgo1 assembly and perturbed CPC centromere localization and function. Our findings reveal that Sgo1 and H3T3ph use the same surface on Survivin to bind CPC. Hence, it is likely that these interactions take place in a spatiotemporally restricted manner, providing a rationale for the Sgo1-mediated "kinetochore-proximal" CPC centromere pool

Human chromosome‐specific aneuploidy is influenced by DNA ‐dependent centromeric features

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