scholarly journals Abscission checkpoint control: stuck in the middle with Aurora B

Open Biology ◽  
2012 ◽  
Vol 2 (7) ◽  
pp. 120095 ◽  
Author(s):  
Mar Carmena
Keyword(s):  
Plasma Membrane ◽  
Cell Division ◽  
Recent Work ◽  
Aurora B ◽  
Checkpoint Control ◽  
Cytoplasmic Bridge ◽  
Division Plane ◽  
Daughter Cells ◽  
Chromosomal Passenger ◽  
Chromatin Bridges

At the end of cell division, the cytoplasmic bridge joining the daughter cells is severed through a process that involves scission of the plasma membrane. The presence of chromatin bridges ‘stuck’ in the division plane is sensed by the chromosomal passenger complex (CPC) component Aurora B kinase, triggering a checkpoint that delays abscission until the chromatin bridges have been resolved. Recent work has started to shed some light on the molecular mechanism by which the CPC controls the timing of abscission.

scholarly journals The Abscission Checkpoint: A Guardian of Chromosomal Stability

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3350
Author(s):  
Eleni Petsalaki ◽  
George Zachos
Keyword(s):  
Mammalian Cells ◽  
Kinase Activity ◽  
Nuclear Pore ◽  
Aurora B ◽  
Intercellular Bridge ◽  
Endosomal Sorting ◽  
Daughter Cells ◽  
Chromosomal Passenger ◽  
Dividing Cells ◽  
Chromatin Bridges

The abscission checkpoint contributes to the fidelity of chromosome segregation by delaying completion of cytokinesis (abscission) when there is chromatin lagging in the intercellular bridge between dividing cells. Although additional triggers of an abscission checkpoint-delay have been described, including nuclear pore defects, replication stress or high intercellular bridge tension, this review will focus only on chromatin bridges. In the presence of such abnormal chromosomal tethers in mammalian cells, the abscission checkpoint requires proper localization and optimal kinase activity of the Chromosomal Passenger Complex (CPC)-catalytic subunit Aurora B at the midbody and culminates in the inhibition of Endosomal Sorting Complex Required for Transport-III (ESCRT-III) components at the abscission site to delay the final cut. Furthermore, cells with an active checkpoint stabilize the narrow cytoplasmic canal that connects the two daughter cells until the chromatin bridges are resolved. Unsuccessful resolution of chromatin bridges in checkpoint-deficient cells or in cells with unstable intercellular canals can lead to chromatin bridge breakage or tetraploidization by regression of the cleavage furrow. In turn, these outcomes can lead to accumulation of DNA damage, chromothripsis, generation of hypermutation clusters and chromosomal instability, which are associated with cancer formation or progression. Recently, many important questions regarding the mechanisms of the abscission checkpoint have been investigated, such as how the presence of chromatin bridges is signaled to the CPC, how Aurora B localization and kinase activity is regulated in late midbodies, the signaling pathways by which Aurora B implements the abscission delay, and how the actin cytoskeleton is remodeled to stabilize intercellular canals with DNA bridges. Here, we review recent progress toward understanding the mechanisms of the abscission checkpoint and its role in guarding genome integrity at the chromosome level, and consider its potential implications for cancer therapy.

scholarly journals The chromosomal passenger complex controls the function of endosomal sorting complex required for transport-III Snf7 proteins during cytokinesis

Open Biology ◽  
2012 ◽  
Vol 2 (5) ◽  
pp. 120070 ◽  
Author(s):  
Luisa Capalbo ◽  
Emilie Montembault ◽  
Tetsuya Takeda ◽  
Zuni I. Bassi ◽  
David M. Glover ◽  
...  
Keyword(s):  
Cell Division ◽  
Molecular Basis ◽  
Cleavage Site ◽  
Human Cells ◽  
Membrane Association ◽  
Aurora B ◽  
Chromosomal Passenger Complex ◽  
Endosomal Sorting ◽  
Daughter Cells ◽  
Chromosomal Passenger

Summary Cytokinesis controls the proper segregation of nuclear and cytoplasmic materials at the end of cell division. The chromosomal passenger complex (CPC) has been proposed to monitor the final separation of the two daughter cells at the end of cytokinesis in order to prevent cell abscission in the presence of DNA at the cleavage site, but the precise molecular basis for this is unclear. Recent studies indicate that abscission could be mediated by the assembly of filaments comprising components of the endosomal sorting complex required for transport-III (ESCRT-III). Here, we show that the CPC subunit Borealin interacts directly with the Snf7 components of ESCRT-III in both Drosophila and human cells. Moreover, we find that the CPC's catalytic subunit, Aurora B kinase, phosphorylates one of the three human Snf7 paralogues—CHMP4C—in its C-terminal tail, a region known to regulate its ability to form polymers and associate with membranes. Phosphorylation at these sites appears essential for CHMP4C function because their mutation leads to cytokinesis defects. We propose that CPC controls abscission timing through inhibition of ESCRT-III Snf7 polymerization and membrane association using two concurrent mechanisms: interaction of its Borealin component with Snf7 proteins and phosphorylation of CHMP4C by Aurora B.

scholarly journals Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis

Open Biology ◽  
2016 ◽  
Vol 6 (10) ◽  
pp. 160248 ◽  
Author(s):  
Luisa Capalbo ◽  
Ioanna Mela ◽  
Maria Alba Abad ◽  
A. Arockia Jeyaprakash ◽  
J. Michael Edwardson ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Cell Division ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Chromosomal Passenger Complex ◽  
Force Microscopy ◽  
Daughter Cells ◽  
Atomic Force ◽  
Chromosomal Passenger

The chromosomal passenger complex (CPC)—composed of Aurora B kinase, Borealin, Survivin and INCENP—surveys the fidelity of genome segregation throughout cell division. The CPC has been proposed to prevent polyploidy by controlling the final separation (known as abscission) of the two daughter cells via regulation of the ESCRT-III CHMP4C component. The molecular details are, however, still unclear. Using atomic force microscopy, we show that CHMP4C binds to and remodels membranes in vitro . Borealin prevents the association of CHMP4C with membranes, whereas Aurora B interferes with CHMP4C's membrane remodelling activity. Moreover, we show that CHMP4C phosphorylation is not required for its assembly into spiral filaments at the abscission site and that two distinctly localized pools of phosphorylated CHMP4C exist during cytokinesis. We also characterized the CHMP4C interactome in telophase cells and show that the centralspindlin complex associates preferentially with unphosphorylated CHMP4C in cytokinesis. Our findings indicate that gradual dephosphorylation of CHMP4C triggers a ‘relay’ mechanism between the CPC and centralspindlin that regulates the timely distribution and activation of CHMP4C for the execution of abscission.

scholarly journals Functional analysis of the chromosomal passenger complex in Arabidopsis

2020 ◽  
Author(s):  
Shinichiro Komaki ◽  
Hidenori Takeuchi ◽  
Yuki Hamamura ◽  
Maren Heese ◽  
Takashi Hashimoto ◽  
...  
Keyword(s):  
Cell Division ◽  
Aurora B ◽  
Division Plane ◽  
Chromosomal Passenger ◽  
Full Complement ◽  
The One ◽  
Sites Of Action ◽  
Chromosome Passenger Complex ◽  
Mitosis And Meiosis ◽  
Kinetochore Function

SUMMARYA key regulator of cell division in all eukaryotes is the kinase Aurora B, which is encoded by the Aurora 3 (AUR3) gene in Arabidopsis. Aurora B has at least two central functions during cell division. On the one hand, it is essential for the correct, i.e. balanced, segregation of chromosomes in mitosis and meiosis by controlling kinetochore function. On the other hand, Aurora B acts at the division plane, where it is necessary to complete cytokinesis. To accomplish these two spatially distinct functions, Aurora B in animals is guided to its sites of action by Borealin, INCENP, and Survivin that build together with Aurora B the chromosome passenger complex (CPC). However, besides Aurora homologs, only a candidate gene with restricted homology to INCENP has so far been described in Arabidopsis raising the question whether there exists a full complement of the CPC in plants and how Aurora homologs are targeted subcellularly. Here, we have identified and functionally characterized a Borealin homolog, BOREALIN RELATED (BORR), in Arabidopsis. This, together with detailed localization studies including the putative Arabidopsis INCENP homolog, supports the existence of a CPC in plants.

scholarly journals Cross-regulation between Aurora B and Citron kinase controls midbody architecture in cytokinesis

Open Biology ◽  
2016 ◽  
Vol 6 (3) ◽  
pp. 160019 ◽  
Author(s):  
Callum McKenzie ◽  
Zuni I. Bassi ◽  
Janusz Debski ◽  
Marco Gottardo ◽  
Giuliano Callaini ◽  
...  
Keyword(s):  
Cell Division ◽  
Molecular Mechanisms ◽  
Coiled Coil ◽  
Aurora B ◽  
Intercellular Bridge ◽  
Daughter Cells ◽  
Chromosomal Passenger ◽  
Citron Kinase ◽  
And Function ◽  
First Time

Cytokinesis culminates in the final separation, or abscission, of the two daughter cells at the end of cell division. Abscission relies on an organelle, the midbody, which forms at the intercellular bridge and is composed of various proteins arranged in a precise stereotypic pattern. The molecular mechanisms controlling midbody organization and function, however, are obscure. Here we show that proper midbody architecture requires cross-regulation between two cell division kinases, Citron kinase (CIT-K) and Aurora B, the kinase component of the chromosomal passenger complex (CPC). CIT-K interacts directly with three CPC components and is required for proper midbody architecture and the orderly arrangement of midbody proteins, including the CPC. In addition, we show that CIT-K promotes Aurora B activity through phosphorylation of the INCENP CPC subunit at the TSS motif. In turn, Aurora B controls CIT-K localization and association with its central spindle partners through phosphorylation of CIT-K's coiled coil domain. Our results identify, for the first time, a cross-regulatory mechanism between two kinases during cytokinesis, which is crucial for establishing the stereotyped organization of midbody proteins.

scholarly journals A complex containing the Sm protein CAR-1 and the RNA helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis elegans

2005 ◽  
Vol 171 (2) ◽  
pp. 267-279 ◽  
Author(s):  
Anjon Audhya ◽  
Francie Hyndman ◽  
Ian X. McLeod ◽  
Amy S. Maddox ◽  
John R. Yates ◽  
...  
Keyword(s):  
Cell Division ◽  
Caenorhabditis Elegans ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Rna Helicase ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Daughter Cells ◽  
Sm Protein ◽  
Spindle Structure

Cytokinesis completes cell division and partitions the contents of one cell to the two daughter cells. Here we characterize CAR-1, a predicted RNA binding protein that is implicated in cytokinesis. CAR-1 localizes to germline-specific RNA-containing particles and copurifies with the essential RNA helicase, CGH-1, in an RNA-dependent fashion. The atypical Sm domain of CAR-1, which directly binds RNA, is dispensable for CAR-1 localization, but is critical for its function. Inhibition of CAR-1 by RNA-mediated depletion or mutation results in a specific defect in embryonic cytokinesis. This cytokinesis failure likely results from an anaphase spindle defect in which interzonal microtubule bundles that recruit Aurora B kinase and the kinesin, ZEN-4, fail to form between the separating chromosomes. Depletion of CGH-1 results in sterility, but partially depleted worms produce embryos that exhibit the CAR-1–depletion phenotype. Cumulatively, our results suggest that CAR-1 functions with CGH-1 to regulate a specific set of maternally loaded RNAs that is required for anaphase spindle structure and cytokinesis.

scholarly journals A Link between Aurora Kinase and Clp1/Cdc14 Regulation Uncovered by the Identification of a Fission Yeast Borealin-Like Protein

2009 ◽  
Vol 20 (16) ◽  
pp. 3646-3659 ◽  
Author(s):  
K. Adam Bohnert ◽  
Jun-Song Chen ◽  
Dawn M. Clifford ◽  
Craig W. Vander Kooi ◽  
Kathleen L. Gould
Keyword(s):  
Cell Division ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Kinase Activity ◽  
Sequence Similarity ◽  
Aurora Kinase ◽  
Genetic Interactions ◽  
Aurora B ◽  
Contractile Ring ◽  
Chromosomal Passenger

The chromosomal passenger complex (CPC) regulates various events in cell division. This complex is composed of a catalytic subunit, Aurora B kinase, and three nonenzymatic subunits, INCENP, Survivin, and Borealin. Together, these four subunits interdependently regulate CPC function, and they are highly conserved among eukaryotes. However, a Borealin homologue has never been characterized in the fission yeast, Schizosaccharomyces pombe . Here, we isolate a previously uncharacterized S. pombe protein through association with the Cdc14 phosphatase homologue, Clp1/Flp1, and identify it as a Borealin-like member of the CPC. Nbl1 (novel Borealin-like 1) physically associates with known CPC components, affects the kinase activity and stability of the S. pombe Aurora B homologue, Ark1, colocalizes with known CPC subunits during mitosis, and shows sequence similarity to human Borealin. Further analysis of the Clp1–Nbl1 interaction indicates that Clp1 requires CPC activity for proper accumulation at the contractile ring (CR). Consistent with this, we describe negative genetic interactions between mutant alleles of CPC and CR components. Thus, this study characterizes a fission yeast Borealin homologue and reveals a previously unrecognized connection between the CPC and the process of cytokinesis in S. pombe .

scholarly journals An ATM–Chk2–INCENP pathway activates the abscission checkpoint

2020 ◽  
Vol 220 (2) ◽  
Author(s):  
Eleni Petsalaki ◽  
George Zachos
Keyword(s):  
Cell Division ◽  
Chromosome Breakage ◽  
Human Cells ◽  
Chromosomal Passenger Complex ◽  
Chromosomal Passenger ◽  
Cultured Human Cells ◽  
Chromatin Bridges

During cell division, in response to chromatin bridges, the chromosomal passenger complex (CPC) delays abscission to prevent chromosome breakage or tetraploidization. Here, we show that inhibition of ATM or Chk2 kinases impairs CPC localization to the midbody center, accelerates midbody resolution in normally segregating cells, and correlates with premature abscission and chromatin breakage in cytokinesis with trapped chromatin. In cultured human cells, ATM activates Chk2 at late midbodies. In turn, Chk2 phosphorylates human INCENP-Ser91 to promote INCENP binding to Mklp2 kinesin and CPC localization to the midbody center through Mklp2 association with Cep55. Expression of truncated Mklp2 that does not bind to Cep55 or nonphosphorylatable INCENP-Ser91A impairs CPC midbody localization and accelerates abscission. In contrast, expression of phosphomimetic INCENP-Ser91D or a chimeric INCENP protein that is targeted to the midbody center rescues the abscission delay in Chk2-deficient or ATM-deficient cells. Furthermore, the Mre11–Rad50–Nbs1 complex is required for ATM activation at the midbody in cytokinesis with chromatin bridges. These results identify an ATM–Chk2–INCENP pathway that imposes the abscission checkpoint by regulating CPC midbody localization.

scholarly journals Delivery of endocytosed proteins to the cell–division plane requires change of pathway from recycling to secretion

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Sandra Richter ◽  
Marika Kientz ◽  
Sabine Brumm ◽  
Mads Eggert Nielsen ◽  
Misoon Park ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Division ◽  
Membrane Trafficking ◽  
Nucleotide Exchange ◽  
Division Plane ◽  
Plant Cytokinesis ◽  
Guanine Nucleotide Exchange ◽  
Cargo Delivery ◽  
Golgi Network ◽  
Cell Division Plane

Membrane trafficking is essential to fundamental processes in eukaryotic life, including cell growth and division. In plant cytokinesis, post-Golgi trafficking mediates a massive flow of vesicles that form the partitioning membrane but its regulation remains poorly understood. Here, we identify functionally redundant Arabidopsis ARF guanine-nucleotide exchange factors (ARF-GEFs) BIG1–BIG4 as regulators of post-Golgi trafficking, mediating late secretion from the trans-Golgi network but not recycling of endocytosed proteins to the plasma membrane, although the TGN also functions as an early endosome in plants. In contrast, BIG1-4 are absolutely required for trafficking of both endocytosed and newly synthesized proteins to the cell–division plane during cytokinesis, counteracting recycling to the plasma membrane. This change from recycling to secretory trafficking pathway mediated by ARF-GEFs confers specificity of cargo delivery to the division plane and might thus ensure that the partitioning membrane is completed on time in the absence of a cytokinesis-interphase checkpoint.

scholarly journals Borealin–nucleosome interaction secures chromosome association of the chromosomal passenger complex

2019 ◽  
Vol 218 (12) ◽  
pp. 3912-3925 ◽  
Author(s):  
Maria A. Abad ◽  
Jan G. Ruppert ◽  
Lana Buzuk ◽  
Martin Wear ◽  
Juan Zou ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Chromosome Association ◽  
Aurora B ◽  
Master Regulator ◽  
Multifaceted Approach ◽  
Chromosomal Passenger Complex ◽  
Chromosome Congression ◽  
Chromosomal Passenger ◽  
And Function

Chromosome association of the chromosomal passenger complex (CPC; consisting of Borealin, Survivin, INCENP, and the Aurora B kinase) is essential to achieve error-free chromosome segregation during cell division. Hence, understanding the mechanisms driving the chromosome association of the CPC is of paramount importance. Here using a multifaceted approach, we show that the CPC binds nucleosomes through a multivalent interaction predominantly involving Borealin. Strikingly, Survivin, previously suggested to target the CPC to centromeres, failed to bind nucleosomes on its own and requires Borealin and INCENP for its binding. Disrupting Borealin–nucleosome interactions excluded the CPC from chromosomes and caused chromosome congression defects. We also show that Borealin-mediated chromosome association of the CPC is critical for Haspin- and Bub1-mediated centromere enrichment of the CPC and works upstream of the latter. Our work thus establishes Borealin as a master regulator determining the chromosome association and function of the CPC.

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