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 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 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.

scholarly journals Phosphorylation at serine 331 is required for Aurora B activation

2011 ◽  
Vol 195 (3) ◽  
pp. 449-466 ◽  
Author(s):  
Eleni Petsalaki ◽  
Tonia Akoumianaki ◽  
Elizabeth J. Black ◽  
David A.F. Gillespie ◽  
George Zachos
Keyword(s):  
Cell Division ◽  
Kinase Activity ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Chromosomal Passenger Complex ◽  
Chromosome Missegregation ◽  
Mitotic Delay ◽  
Chromosomal Passenger ◽  
Spontaneous Chromosome ◽  
Chk1 Kinase

Aurora B kinase activity is required for successful cell division. In this paper, we show that Aurora B is phosphorylated at serine 331 (Ser331) during mitosis and that phosphorylated Aurora B localizes to kinetochores in prometaphase cells. Chk1 kinase is essential for Ser331 phosphorylation during unperturbed prometaphase or during spindle disruption by taxol but not nocodazole. Phosphorylation at Ser331 is required for optimal phosphorylation of INCENP at TSS residues, for Survivin association with the chromosomal passenger complex, and for complete Aurora B activation, but it is dispensable for Aurora B localization to centromeres, for autophosphorylation at threonine 232, and for association with INCENP. Overexpression of Aurora BS331A, in which Ser331 is mutated to alanine, results in spontaneous chromosome missegregation, cell multinucleation, unstable binding of BubR1 to kinetochores, and impaired mitotic delay in the presence of taxol. We propose that Chk1 phosphorylates Aurora B at Ser331 to fully induce Aurora B kinase activity. These results indicate that phosphorylation at Ser331 is an essential mechanism for Aurora B activation.

Cell division control by the Chromosomal Passenger Complex

2012 ◽  
Vol 318 (12) ◽  
pp. 1407-1420 ◽  
Author(s):  
Maike S. van der Waal ◽  
Rutger C.C. Hengeveld ◽  
Armando van der Horst ◽  
Susanne M.A. Lens
Keyword(s):  
Cell Division ◽  
Chromosomal Passenger Complex ◽  
Chromosomal Passenger ◽  
Cell Division Control

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 The chromosomal passenger complex: guiding Aurora-B through mitosis

2006 ◽  
Vol 173 (6) ◽  
pp. 833-837 ◽  
Author(s):  
Gerben Vader ◽  
René H. Medema ◽  
Susanne M.A. Lens
Keyword(s):  
Cell Division ◽  
Histone Modification ◽  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Aurora B ◽  
Chromosomal Passenger Complex ◽  
Precise Control ◽  
Chromosome Alignment ◽  
Chromosomal Passenger ◽  
And Function

During mitosis, the chromosomal passenger complex (CPC) orchestrates highly different processes, such as chromosome alignment, histone modification, and cytokinesis. Proper and timely localization of this complex is the key to precise control over the enzymatic core of the CPC, the Aurora-B kinase. We discuss the molecular mechanisms by which the CPC members direct the dynamic localization of the complex throughout cell division. Also, we summarize posttranslational modifications that occur on the CPC and discuss their roles in regulating localization and function of this mitotic complex.

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.

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