scholarly journals Abscission Checkpoint Bodies Reveal a New Facet of Abscission Checkpoint Control

2020 ◽  
Author(s):  
Lauren K. Williams ◽  
Douglas R. Mackay ◽  
Madeline A. Whitney ◽  
Wesley I. Sundquist ◽  
Katharine S. Ullman
Keyword(s):  
Cell Types ◽  
Aurora B ◽  
Genomic Integrity ◽  
Checkpoint Control ◽  
Nuclear Speckles ◽  
Aurora B Kinase ◽  
Multiple Targets ◽  
Membrane Fission ◽  
Interchromatin Granules

AbstractThe abscission checkpoint regulates the ESCRT membrane fission machinery and thereby delays cytokinetic abscission to protect genomic integrity in response to residual mitotic errors. The checkpoint is maintained by Aurora B kinase, which phosphorylates multiple targets, including CHMP4C, a regulatory ESCRT-III subunit necessary for this checkpoint. We now report the discovery that cytoplasmic abscission checkpoint bodies (ACBs) containing phospho-Aurora B and tri-phospho-CHMP4C develop in telophase under an active checkpoint. ACBs are derived from Mitotic Interchromatin Granules (MIGs), transient mitotic structures whose components are housed in splicing-related nuclear speckles during interphase. ACB formation requires CHMP4C, and the ESCRT factor ALIX also contributes. ACB formation is conserved across cell types and under multiple circumstances that activate the checkpoint. Finally, ACBs retain a population of ALIX, and their presence correlates with delayed recruitment of ALIX to the midbody where it would normally promote abscission. Thus, a cytoplasmic mechanism helps regulate midbody machinery to delay abscission.

scholarly journals Identification of abscission checkpoint bodies as structures that regulate ESCRT factors to control abscission timing

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Lauren K Williams ◽  
Douglas R Mackay ◽  
Madeline A Whitney ◽  
Genevieve C Couldwell ◽  
Wesley I Sundquist ◽  
...  
Keyword(s):  
Cell Types ◽  
Aurora B ◽  
Genomic Integrity ◽  
Nuclear Speckles ◽  
Aurora B Kinase ◽  
Multiple Targets ◽  
Membrane Fission ◽  
Interchromatin Granules

The abscission checkpoint regulates the ESCRT membrane fission machinery and thereby delays cytokinetic abscission to protect genomic integrity in response to residual mitotic errors. The checkpoint is maintained by Aurora B kinase, which phosphorylates multiple targets, including CHMP4C, a regulatory ESCRT-III subunit necessary for this checkpoint. We now report the discovery that cytoplasmic abscission checkpoint bodies (ACBs) containing phospho-Aurora B and tri-phospho-CHMP4C develop during an active checkpoint. ACBs are derived from Mitotic Interchromatin Granules (MIGs), transient mitotic structures whose components are housed in splicing-related nuclear speckles during interphase. ACB formation requires CHMP4C, and the ESCRT factor ALIX also contributes. ACB formation is conserved across cell types and under multiple circumstances that activate the checkpoint. Finally, ACBs retain a population of ALIX, and their presence correlates with delayed abscission and delayed recruitment of ALIX to the midbody where it would normally promote abscission. Thus, a cytoplasmic mechanism helps regulate midbody machinery to delay abscission.

scholarly journals Aurora B–mediated localized delays in nuclear envelope formation facilitate inclusion of late-segregating chromosome fragments

2015 ◽  
Vol 26 (12) ◽  
pp. 2227-2241 ◽  
Author(s):  
Travis Karg ◽  
Brandt Warecki ◽  
William Sullivan
Keyword(s):  
Nuclear Envelope ◽  
Chromosome Segregation ◽  
Daughter Nucleus ◽  
Kinase Activity ◽  
Aurora B ◽  
Genomic Integrity ◽  
Aurora B Kinase ◽  
Chromosome Fragments ◽  
Nuclear Envelope Formation

To determine how chromosome segregation is coordinated with nuclear envelope formation (NEF), we examined the dynamics of NEF in the presence of lagging acentric chromosomes in Drosophila neuroblasts. Acentric chromosomes often exhibit delayed but ultimately successful segregation and incorporation into daughter nuclei. However, it is unknown whether these late-segregating acentric fragments influence NEF to ensure their inclusion in daughter nuclei. Through live analysis, we show that acentric chromosomes induce highly localized delays in the reassembly of the nuclear envelope. These delays result in a gap in the nuclear envelope that facilitates the inclusion of lagging acentrics into telophase daughter nuclei. Localized delays of nuclear envelope reassembly require Aurora B kinase activity. In cells with reduced Aurora B activity, there is a decrease in the frequency of local nuclear envelope reassembly delays, resulting in an increase in the frequency of acentric-bearing, lamin-coated micronuclei. These studies reveal a novel role of Aurora B in maintaining genomic integrity by promoting the formation of a passageway in the nuclear envelope through which late-segregating acentric chromosomes enter the telophase daughter nucleus.

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 Aurora B kinase activation requires survivin priming phosphorylation by PLK1

2010 ◽  
Vol 3 (4) ◽  
pp. 260-267 ◽  
Author(s):  
Youjun Chu ◽  
Phil Y. Yao ◽  
Wenwen Wang ◽  
Dongmei Wang ◽  
Zhikai Wang ◽  
...  
Keyword(s):  
Aurora B ◽  
Aurora B Kinase ◽  
Kinase Activation

scholarly journals Enhancement of radiation response in p53-deficient cancer cells by the Aurora-B kinase inhibitor AZD1152

Oncogene ◽  
2007 ◽  
Vol 27 (23) ◽  
pp. 3244-3255 ◽  
Author(s):  
Y Tao ◽  
P Zhang ◽  
F Girdler ◽  
V Frascogna ◽  
M Castedo ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Kinase Inhibitor ◽  
Radiation Response ◽  
Aurora B ◽  
Aurora B Kinase
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