scholarly journals Nbl1p: A Borealin/Dasra/CSC-1-like Protein Essential for Aurora/Ipl1 Complex Function and Integrity in Saccharomyces cerevisiae

2009 ◽  
Vol 20 (6) ◽  
pp. 1772-1784 ◽  
Author(s):  
Yuko Nakajima ◽  
Randall G. Tyers ◽  
Catherine C.L. Wong ◽  
John R. Yates ◽  
David G. Drubin ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Complex Function ◽  
Aurora Kinase ◽  
Aurora B ◽  
Protein Structure Modeling ◽  
Homology Searching ◽  
Chromosomal Passenger ◽  
And Function ◽  
Computational Analyses ◽  
Related Proteins

The Aurora kinase complex, also called the chromosomal passenger complex (CPC), is essential for faithful chromosome segregation and completion of cell division. In Fungi and Animalia, this complex consists of the kinase Aurora B/AIR-2/Ipl1p, INCENP/ICP-1/Sli15p, and Survivin/BIR-1/Bir1p. A fourth subunit, Borealin/Dasra/CSC-1, is required for CPC targeting to centromeres and central spindles and has only been found in Animalia. Here we identified a new core component of the CPC in budding yeast, Nbl1p. NBL1 is essential for viability and nbl1 mutations cause chromosome missegregation and lagging chromosomes. Nbl1p colocalizes and copurifies with the CPC, and it is essential for CPC localization, stability, integrity, and function. Nbl1p is related to the N-terminus of Borealin/Dasra/CSC-1 and is similarly involved in connecting the other CPC subunits. Distant homology searching identified nearly 200, mostly unannotated, Borealin/Dasra/CSC-1–related proteins from nearly 150 species within Fungi and Animalia. Analysis of the sequence of these proteins, combined with comparative protein structure modeling of Bir1p-Nbl1p-Sli15p using the crystal structure of the human Survivin–Borealin–INCENP complex, revealed a striking structural conservation across a broad range of species. Our biological and computational analyses therefore establish that the fundamental design of the CPC is conserved from Fungi to Animalia.

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 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 Bub1, Sgo1, and Mps1 mediate a distinct pathway for chromosome biorientation in budding yeast

2011 ◽  
Vol 22 (9) ◽  
pp. 1473-1485 ◽  
Author(s):  
Zuzana Storchová ◽  
Justin S. Becker ◽  
Nicolas Talarek ◽  
Sandra Kögelsberger ◽  
David Pellman
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Budding Yeast ◽  
Spindle Pole ◽  
Growth Defect ◽  
Aurora B ◽  
Mitotic Kinase ◽  
Sister Chromatids ◽  
Chromosome Alignment ◽  
Chromosomal Passenger

The conserved mitotic kinase Bub1 performs multiple functions that are only partially characterized. Besides its role in the spindle assembly checkpoint and chromosome alignment, Bub1 is crucial for the kinetochore recruitment of multiple proteins, among them Sgo1. Both Bub1 and Sgo1 are dispensable for growth of haploid and diploid budding yeast, but they become essential in cells with higher ploidy. We find that overexpression of SGO1 partially corrects the chromosome segregation defect of bub1Δ haploid cells and restores viability to bub1Δ tetraploid cells. Using an unbiased high-copy suppressor screen, we identified two members of the chromosomal passenger complex (CPC), BIR1 (survivin) and SLI15 (INCENP, inner centromere protein), as suppressors of the growth defect of both bub1Δ and sgo1Δ tetraploids, suggesting that these mutants die due to defects in chromosome biorientation. Overexpression of BIR1 or SLI15 also complements the benomyl sensitivity of haploid bub1Δ and sgo1Δ cells. Mutants lacking SGO1 fail to biorient sister chromatids attached to the same spindle pole (syntelic attachment) after nocodazole treatment. Moreover, the sgo1Δ cells accumulate syntelic attachments in unperturbed mitoses, a defect that is partially corrected by BIR1 or SLI15 overexpression. We show that in budding yeast neither Bub1 nor Sgo1 is required for CPC localization or affects Aurora B activity. Instead we identify Sgo1 as a possible partner of Mps1, a mitotic kinase suggested to have an Aurora B–independent function in establishment of biorientation. We found that Sgo1 overexpression rescues defects caused by metaphase inactivation of Mps1 and that Mps1 is required for Sgo1 localization to the kinetochore. We propose that Bub1, Sgo1, and Mps1 facilitate chromosome biorientation independently of the Aurora B–mediated pathway at the budding yeast kinetochore and that both pathways are required for the efficient turnover of syntelic attachments.

scholarly journals A single amino acid change converts Aurora-A into Aurora-B-like kinase in terms of partner specificity and cellular function

2009 ◽  
Vol 106 (17) ◽  
pp. 6939-6944 ◽  
Author(s):  
Jingyan Fu ◽  
Minglei Bian ◽  
Junjun Liu ◽  
Qing Jiang ◽  
Chuanmao Zhang
Keyword(s):  
Amino Acid ◽  
Aurora Kinase ◽  
Single Amino Acid ◽  
Aurora B ◽  
Aurora A ◽  
Single Amino Acid Residue ◽  
Single Amino Acid Change ◽  
Equivalent Residue ◽  
And Function

Aurora kinase-A and -B are key regulators of the cell cycle and tumorigenesis. It has remained a mystery why these 2 Aurora kinases, although highly similar in protein sequence and structure, are distinct in subcellular localization and function. Here, we report the striking finding that a single amino acid residue is responsible for these differences. We replaced the Gly-198 of Aurora-A with the equivalent residue Asn-142 of Aurora-B and found that in HeLa cells, Aurora-AG198N was recruited to the inner centromere in metaphase and the midzone in anaphase, reminiscent of the Aurora-B localization. Moreover, Aurora-AG198N compensated for the loss of Aurora-B in chromosome misalignment and cell premature exit from mitosis. Furthermore, Aurora-AG198N formed a complex with the Aurora-B partners, INCENP and Survivin, and its localization depended on this interaction. Aurora-AG198N phosphorylated the Aurora-B substrates INCENP and Survivin in vitro. Therefore, we propose that the presence of Gly or Asn at a single site assigns Aurora-A and -B to their respective partners and thus to their distinctive subcellular localizations and functions.

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 The aurora kinase AIR-2 functions in the release of chromosome cohesion in Caenorhabditis elegans meiosis

2002 ◽  
Vol 157 (2) ◽  
pp. 219-229 ◽  
Author(s):  
Eric Rogers ◽  
John D. Bishop ◽  
James A. Waddle ◽  
Jill M. Schumacher ◽  
Rueyling Lin
Keyword(s):  
Caenorhabditis Elegans ◽  
Chromosome Segregation ◽  
Aurora Kinase ◽  
Aurora B ◽  
Localization Pattern ◽  
Meiotic Chromosomes ◽  
Sister Chromatids ◽  
Chromosome Separation ◽  
Major Amino Acid

Accurate chromosome segregation during cell division requires not only the establishment, but also the precise, regulated release of chromosome cohesion. Chromosome dynamics during meiosis are more complicated, because homologues separate at anaphase I whereas sister chromatids remain attached until anaphase II. How the selective release of chromosome cohesion is regulated during meiosis remains unclear. We show that the aurora-B kinase AIR-2 regulates the selective release of chromosome cohesion during Caenorhabditis elegans meiosis. AIR-2 localizes to subchromosomal regions corresponding to last points of contact between homologues in metaphase I and between sister chromatids in metaphase II. Depletion of AIR-2 by RNA interference (RNAi) prevents chromosome separation at both anaphases, with concomitant prevention of meiotic cohesin REC-8 release from meiotic chromosomes. We show that AIR-2 phosphorylates REC-8 at a major amino acid in vitro. Interestingly, depletion of two PP1 phosphatases, CeGLC-7α and CeGLC-7β, abolishes the restricted localization pattern of AIR-2. In Ceglc-7α/β(RNAi) embryos, AIR-2 is detected on the entire bivalent. Concurrently, chromosomal REC-8 is dramatically reduced and sister chromatids are separated precociously at anaphase I in Ceglc-7α/β(RNAi) embryos. We propose that AIR-2 promotes the release of chromosome cohesion via phosphorylation of REC-8 at specific chromosomal locations and that CeGLC-7α/β, directly or indirectly, antagonize AIR-2 activity.

scholarly journals Molecular Basis for CPC-Sgo1 Interaction: Implications for Centromere Localisation and Function of the CPC

2021 ◽  
Author(s):  
Maria Alba Abad ◽  
Tanmay Gupta ◽  
Michael A Hadders ◽  
Amanda Meppelink ◽  
J Pepijn Wopken ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Molecular Basis ◽  
Hot Spot ◽  
Histone H3 ◽  
Direct Interaction ◽  
Histone H2a ◽  
Chromosomal Passenger ◽  
And Function ◽  
Affinity Interaction

AbstractThe Chromosomal Passenger Complex (CPC; consisting of Borealin, Survivin, INCENP and Aurora B kinase) and Shugoshin 1 (Sgo1) are key regulators of chromosome bi-orientation, a process essential for error-free chromosome segregation. Their functions rely on their ability to associate with centromeres. Two histone phosphorylations, histone H3 Thr3 (H3T3ph; directly recognised by Survivin) and histone H2A Thr120 (H2AT120ph; indirectly recognised via Sgo1), together with CPC’s intrinsic ability to bind nucleosome, facilitate CPC centromere recruitment. The molecular basis for CPC-Sgo1 binding and how their direct interaction influences CPC centromere localisation and function are lacking. Here, using an integrative structure-function approach, we show that the histone H3-like Sgo1 N-terminal tail interacts with Survivin acting as a hot-spot for CPC-Sgo1 assembly, while downstream Sgo1 residues, mainly with Borealin contributes for high affinity interaction. Disruption of the Sgo1 N-terminal tail-Survivin interaction abolished CPC-Sgo1 assembly in vitro and perturbed centromere localisation and function of CPC. Our findings provide evidence that CPC binding to Sgo1 and histone H3 N-terminal tail are mutually exclusive, suggesting that these interactions will likely take place in a spatially/temporally restricted manner and provide a rationale for the Sgo1-mediated ‘kinetochore proximal centromere’ pool of CPC.

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.

Megakaryocytes express functional Aurora-B kinase in endomitosis

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 1017-1024 ◽  
Author(s):  
Amy E. Geddis ◽  
Kenneth Kaushansky
Keyword(s):  
Aurora Kinase ◽  
Aurora B ◽  
Aurora A Kinase ◽  
Aurora B Kinase ◽  
Late Anaphase ◽  
Chromosomal Passenger ◽  
Early Anaphase ◽  
Chromosomal Passenger Proteins ◽  
Diploid Cells ◽  
Passenger Proteins

AbstractEndomitosis (EnM) in megakaryocytes (MKs) is characterized by abortion of mitosis in late anaphase and failure of cytokinesis; subsequent reinitiation of DNA synthesis results in polyploidy. Ablation of chromosomal passenger proteins including Aurora-B kinase causes defects in late anaphase and cytokinesis in diploid cells; thus one hypothesis is that the expression or function of these proteins in polyploid MKs is abnormal. It has been reported that Aurora-B kinase mRNA is decreased in polyploid megakaryocytic cells, suggesting that deficiency of Aurora-B kinase is responsible for EnM. We examined the localization of Aurora-B kinase and additional members of the chromosomal passenger protein and aurora kinase families in MKs. We found that in EnM MKs (1) Aurora-B kinase is present and appropriately localized to centromeres in early EnM; (2) in low-ploidy human MKs, centromeric localization of survivin and inner centromere protein (INCENP) can also be demonstrated; (3) the function of Aurora-B kinase, as measured by Ser10 phosphorylation of histone H3, is intact; and (4) aurora-A kinase localizes appropriately to centrosomes in EnM. These results suggest that EnM MKs appropriately express functional Aurora-B kinase and related proteins in early anaphase, making a simple deficiency of this protein an unlikely explanation for polyploidy in this cell type.

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.

Sign in / Sign up

Export Citation Format

Share Document