scholarly journals Haspin participates in Aurora phosphorylation at centromeres and contributes to chromosome congression in male mouse meiosis

2021 ◽  
Author(s):  
Ines Berenguer ◽  
Pablo Lopez Jimenez ◽  
Irene Mena ◽  
Alberto Viera ◽  
Jesus Page ◽  
...  
Keyword(s):  
Relevant Information ◽  
Male Meiosis ◽  
Histone Mark ◽  
Aurora B ◽  
Genetic Mouse Model ◽  
Chromosome Congression ◽  
Chromosomal Passenger ◽  
Mitosis And Meiosis

Chromosome segregation requires that centromeres properly attach to spindle microtubules. This is an essential step towards the accuracy of cell division and therefore must be precisely regulated in both mitosis and meiosis. One of the main centromeric regulatory signaling pathways is the Haspin-H3T3ph-chromosomal passenger complex (CPC) cascade, which is responsible for the recruitment of the CPC to the centromeres. In mitosis, Haspin kinase phosphorylates H3 at threonine 3 (H3T3ph), the essential histone mark that recruits the CPC whose catalytic component is Aurora B kinase. To date, no data has yet been presented about the action of the centromeric Haspin-H3T3ph-CPC pathway in mammalian male meiosis. We have analyzed the consequences of Haspin chemical inhibition in cultured spermatocytes using LDN-192960. Our in vitro studies suggest that Haspin kinase activity is required for proper chromosome congression during both meiotic divisions and for the recruitment of phosphorylated Aurora B at meiotic centromeres. These results have been confirmed by the characterization of the meiotic phenotype of the genetic mouse model Haspin-/-, which displays similar defects. In addition, our work demonstrates that the absence of H3T3ph histone mark does not alter SGO2 localization to meiotic centromeres. These results add new and relevant information regarding the regulation of centromere function during meiosis.

scholarly journals RanBP2 and SENP3 Function in a Mitotic SUMO2/3 Conjugation-Deconjugation Cycle on Borealin

2009 ◽  
Vol 20 (1) ◽  
pp. 410-418 ◽  
Author(s):  
Ulf R. Klein ◽  
Markus Haindl ◽  
Erich A. Nigg ◽  
Stefan Muller
Keyword(s):  
Mammalian Cells ◽  
Spindle Assembly Checkpoint ◽  
Critical Role ◽  
Specific Interaction ◽  
Regulatory Function ◽  
Mitotic Progression ◽  
Chromosome Congression ◽  
Chromosomal Passenger

The ubiquitin-like SUMO system controls cellular key functions, and several lines of evidence point to a critical role of SUMO for mitotic progression. However, in mammalian cells mitotic substrates of sumoylation and the regulatory components involved are not well defined. Here, we identify Borealin, a component of the chromosomal passenger complex (CPC), as a mitotic target of SUMO. The CPC, which additionally comprises INCENP, Survivin, and Aurora B, regulates key mitotic events, including chromosome congression, the spindle assembly checkpoint, and cytokinesis. We show that Borealin is preferentially modified by SUMO2/3 and demonstrate that the modification is dynamically regulated during mitotic progression, peaking in early mitosis. Intriguingly, the SUMO ligase RanBP2 interacts with the CPC, stimulates SUMO modification of Borealin in vitro, and is required for its modification in vivo. Moreover, the SUMO isopeptidase SENP3 is a specific interaction partner of Borealin and catalyzes the removal of SUMO2/3 from Borealin. These data thus delineate a mitotic SUMO2/3 conjugation–deconjugation cycle of Borealin and further assign a regulatory function of RanBP2 and SENP3 in the mitotic SUMO pathway.

scholarly journals Centromere Targeting of the Chromosomal Passenger Complex Requires a Ternary Subcomplex of Borealin, Survivin, and the N-Terminal Domain of INCENP

2006 ◽  
Vol 17 (6) ◽  
pp. 2547-2558 ◽  
Author(s):  
Ulf R. Klein ◽  
Erich A. Nigg ◽  
Ulrike Gruneberg
Keyword(s):  
Functional Module ◽  
Aurora B ◽  
Serine Threonine Kinase ◽  
Chromosomal Passenger Complex ◽  
Chromosomal Passenger ◽  
Core Components ◽  
Interfering Rna ◽  
Centromere Assembly

The chromosomal passenger complex (CPC), consisting of the serine/threonine kinase Aurora B, the inner centromere protein INCENP, Survivin, and Borealin/DasraB, has essential functions at the centromere in ensuring correct chromosome alignment and segregation. Despite observations that small interfering RNA-mediated knockdown of any one member of the CPC abolishes localization of the other subunits, it remains unclear how the complex is targeted to the centromere. We have now identified a ternary subcomplex of the CPC comprising Survivin, Borealin, and the N-terminal 58 amino acids of INCENP in vitro and in vivo. This subcomplex was found to be essential and sufficient for targeting to the centromere. Notably, Aurora B kinase, the enzymatic core of the CPC, was not required for centromere localization of the subcomplex. We demonstrate that CPC targeting to the centromere does not depend on CENP-A and hMis12, two core components for kinetochore/centromere assembly, and provide evidence that the CPC may be directed to centromeric DNA directly via the Borealin subunit. Our findings thus establish a functional module within the CPC that assembles on the N terminus of INCENP and controls centromere recruitment.

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 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 The COMA complex interacts with Cse4 and positions Sli15/Ipl1 at the budding yeast inner kinetochore

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Josef Fischböck-Halwachs ◽  
Sylvia Singh ◽  
Mia Potocnjak ◽  
Götz Hagemann ◽  
Victor Solis-Mezarino ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Synthetic Lethality ◽  
Protein Complexes ◽  
Budding Yeast ◽  
Molecular Characteristics ◽  
Aurora B ◽  
C Terminus ◽  
Chromosomal Passenger ◽  
Macromolecular Protein

Kinetochores are macromolecular protein complexes at centromeres that ensure accurate chromosome segregation by attaching chromosomes to spindle microtubules and integrating safeguard mechanisms. The inner kinetochore is assembled on CENP-A nucleosomes and has been implicated in establishing a kinetochore-associated pool of Aurora B kinase, a chromosomal passenger complex (CPC) subunit, which is essential for chromosome biorientation. By performing crosslink-guided in vitro reconstitution of budding yeast kinetochore complexes we showed that the Ame1/Okp1CENP-U/Q heterodimer, which forms the COMA complex with Ctf19/Mcm21CENP-P/O, selectively bound Cse4CENP-A nucleosomes through the Cse4 N-terminus. The Sli15/Ipl1INCENP/Aurora-B core-CPC interacted with COMA in vitro through the Ctf19 C-terminus whose deletion affected chromosome segregation fidelity in Sli15 wild-type cells. Tethering Sli15 to Ame1/Okp1 rescued synthetic lethality upon Ctf19 depletion in a Sli15 centromere-targeting deficient mutant. This study shows molecular characteristics of the point-centromere kinetochore architecture and suggests a role for the Ctf19 C-terminus in mediating CPC-binding and accurate chromosome segregation.

scholarly journals The Cul3–KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis

2009 ◽  
Vol 187 (6) ◽  
pp. 791-800 ◽  
Author(s):  
Sarah Maerki ◽  
Michael H. Olma ◽  
Titu Staubli ◽  
Patrick Steigemann ◽  
Daniel W. Gerlich ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Ubiquitin Ligases ◽  
Aurora B ◽  
Chromosomal Passenger Complex ◽  
Chromosome Alignment ◽  
Chromosomal Passenger ◽  
Spindle Midzone ◽  
Broad Complex

Cul3 (Cullin3)-based E3 ubiquitin ligases recently emerged as critical regulators of mitosis. In this study, we identify two mammalian BTB (Bric-a-brac–Tramtrack–Broad complex)-Kelch proteins, KLHL21 and KLHL22, that interact with Cul3 and are required for efficient chromosome alignment. Interestingly, KLHL21 but not KLHL22 is necessary for cytokinesis and regulates translocation of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase, similar to the previously described BTB-Kelch proteins KLHL9 and KLHL13. KLHL21 directly binds to Aurora B and mediates ubiquitination of Aurora B in vitro. In contrast to KLHL9 and KLHL13, KLHL21 localizes to midzone microtubules in anaphase and recruits Aurora B and Cul3 to this region. Together, our results suggest that different Cul3 adaptors nonredundantly regulate Aurora B during mitosis, possibly by ubiquitinating different pools of Aurora B at distinct subcellular localizations.

scholarly journals Establishing correct kinetochore-microtubule attachments in mitosis and meiosis

2020 ◽  
Vol 64 (2) ◽  
pp. 277-287
Author(s):  
Gisela Cairo ◽  
Soni Lacefield
Keyword(s):  
Error Correction ◽  
Chromosome Segregation ◽  
Germ Cells ◽  
Chromosomal Localization ◽  
Aurora B ◽  
Molecular Pathways ◽  
Human Cell Lines ◽  
Chromosomal Passenger ◽  
Spindle Microtubules ◽  
Mitosis And Meiosis

Abstract Faithful chromosome segregation in mitosis and meiosis requires that chromosomes properly attach to spindle microtubules. Initial kinetochore-microtubule attachments are often incorrect and rely on error correction mechanisms to release improper attachments, allowing the formation of new attachments. Aurora B kinase and, in mammalian germ cells, Aurora C kinase function as the enzymatic component of the Chromosomal Passenger Complex (CPC), which localizes to the inner centromere/kinetochore and phosphorylates kinetochore proteins for microtubule release during error correction. In this review, we discuss recent findings of the molecular pathways that regulate the chromosomal localization of Aurora B and C kinases in human cell lines, mice, fission yeast, and budding yeast. We also discuss differences in the importance of localization pathways between mitosis and meiosis.

scholarly journals Direct Nucleosome Binding of Borealin Secures Chromosome Association and Function of the Chromosomal Passenger complex

2019 ◽  
Author(s):  
M. A. Abad ◽  
J. G. Ruppert ◽  
L. Buzuk ◽  
M. Wear ◽  
J. Zou ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Chromosome Association ◽  
Aurora B ◽  
Multifaceted Approach ◽  
Chromosomal Passenger Complex ◽  
Chromosome Congression ◽  
Chromosomal Passenger ◽  
And Function ◽  
Nucleosome Binding

SummaryChromosome 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 [1–3] 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 The COMA complex is required for positioning Ipl1 activity proximal to Cse4 nucleosomes in budding yeast

2018 ◽  
Author(s):  
Josef Fischböck Halwachs ◽  
Sylvia Singh ◽  
Mia Potocnjak ◽  
Götz Hagemann ◽  
Victor Solis ◽  
...  
Keyword(s):  
Synthetic Lethality ◽  
Protein Complexes ◽  
Budding Yeast ◽  
Aurora B ◽  
Control Mechanisms ◽  
C Terminus ◽  
Chromosomal Passenger ◽  
A Subunit ◽  
Macromolecular Protein

AbstractKinetochores are macromolecular protein complexes assembled on centromeric chromatin that ensure accurate chromosome segregation by linking DNA to spindle microtubules and integrating safeguard mechanisms. A kinetochore-associated pool of Ipl1Aurora B kinase, a subunit of the chromosomal passenger complex (CPC), was previously implicated in feedback control mechanisms. To study the kinetochore subunit connectivity built on budding yeast point centromeres and its CPC interactions we performed crosslink-guided in vitro reconstitution. The Ame1/Okp1CENP-U/Q heterodimer, forming the COMA complex with Ctf19/Mcm21CENP-P/O, selectively bound Cse4CENP-A nucleosomes through the Cse4 N-terminus and thereby establishes a direct link to the outer kinetochore MTW1 complex. The Sli15/Ipl1INCENP/Aurora B core-CPC interacted with COMA through the Ctf19 C-terminus, and artificial tethering of Sli15 to Ame1/Okp1 rescued synthetic lethality upon Ctf19/Mcm21 deletion in a Sli15 centromere-targeting deficient mutant. This study reveals characteristics of the inner kinetochore architecture assembled at point centromeres and the relevance of its Sli15/Ipl1 interaction for CPC function.

Sign in / Sign up

Export Citation Format

Share Document