scholarly journals Shugoshin biases chromosomes for biorientation through condensin recruitment to the pericentromere

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Kitty F Verzijlbergen ◽  
Olga O Nerusheva ◽  
David Kelly ◽  
Alastair Kerr ◽  
Dean Clift ◽  
...  
Keyword(s):  
Error Correction ◽  
Molecular Basis ◽  
Budding Yeast ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Dual Roles ◽  
Sister Kinetochore

To protect against aneuploidy, chromosomes must attach to microtubules from opposite poles (‘biorientation’) prior to their segregation during mitosis. Biorientation relies on the correction of erroneous attachments by the aurora B kinase, which destabilizes kinetochore-microtubule attachments that lack tension. Incorrect attachments are also avoided because sister kinetochores are intrinsically biased towards capture by microtubules from opposite poles. Here, we show that shugoshin acts as a pericentromeric adaptor that plays dual roles in biorientation in budding yeast. Shugoshin maintains the aurora B kinase at kinetochores that lack tension, thereby engaging the error correction machinery. Shugoshin also recruits the chromosome-organizing complex, condensin, to the pericentromere. Pericentromeric condensin biases sister kinetochores towards capture by microtubules from opposite poles. Our findings uncover the molecular basis of the bias to sister kinetochore capture and expose shugoshin as a pericentromeric hub controlling chromosome biorientation.

scholarly journals chTOG is a conserved mitotic error correction factor

2020 ◽  
Author(s):  
Jacob A. Herman ◽  
Matthew P. Miller ◽  
Sue Biggins
Keyword(s):  
Protein Kinase ◽  
Error Correction ◽  
Chromosome Segregation ◽  
Correction Factor ◽  
Budding Yeast ◽  
Aurora B ◽  
Spindle Poles ◽  
Low Tension ◽  
Intrinsic Error

AbstractAccurate chromosome segregation requires kinetochores on duplicated chromatids to biorient by attaching to dynamic microtubules from opposite spindle poles, which exerts forces to bring kinetochores under tension. However, kinetochores initially bind to MTs indiscriminately, resulting in errors that must be corrected. While the Aurora B protein kinase destabilizes low-tension attachments by phosphorylating kinetochores, low-tension attachments are intrinsically less stable than those under higher tension in vitro independent of Aurora activity. Intrinsic tensionsensitive behavior requires the microtubule regulator Stu2 (budding yeast Dis1/XMAP215 ortholog), which we demonstrate here is likely a conserved function for the TOG protein family. The human TOG protein, chTOG, localizes to kinetochores independent of microtubules by interacting with Hec1. We identify a chTOG mutant that regulates microtubule dynamics but accumulates erroneous kinetochore-microtubule attachments that Aurora B fails to destabilize. Thus, TOG proteins confer a unique, intrinsic error correction activity to kinetochores that ensures accurate chromosome segregation.

scholarly journals Aurora B-INCENP localization at centromeres/inner kinetochores is essential for chromosome bi-orientation in budding yeast

2019 ◽  
Author(s):  
Luis J Garcia-Rodriguez ◽  
Taciana Kasciukovic ◽  
Viola Denninger ◽  
Tomoyuki U Tanaka
Keyword(s):  
Budding Yeast ◽  
Aurora B ◽  
Dependent Manner ◽  
Aurora B Kinase ◽  
Insight Into

To promote chromosome bi-orientation, Aurora B kinase weakens and disrupts aberrant kinetochore-MT interaction. It has long been debated how Aurora B halts this action when bi-orientation is established and tension is applied across sister kinetochores. Pertinent to this debate, it was shown that Bir1 (yeast Survivin), which recruits Ipl1-Sli15 (yeast Aurora B-INCENP) to centromeres, is dispensable for bi-orientation, raising the possibility that Aurora B localization at centromeres is not required for bi-orientation. Here, we show that the COMA inner kinetochore sub-complex physically interacts with Sli15, recruits Ipl1-Sli15 to the inner kinetochore and promotes chromosome bi-orientation, independently of Bir1, in budding yeast. Moreover, using an engineered recruitment of Ipl1-Sli15 to the inner kinetochore when both Bir1 and COMA are defective, we show that localization of Ipl1-Sli15 at centromeres/inner kinetochores is essential for bi-orientation, refuting the above possibility. Our results give important insight into how Aurora B disrupts kinetochore-MT interaction in a tension-dependent manner, to promote chromosome bi-orientation.

scholarly journals Kinetochore-associated Mps1 regulates the strength of kinetochore-microtubule attachments via Ndc80 phosphorylation

2021 ◽  
Author(s):  
Krishna K. Sarangapani ◽  
Lori B. Koch ◽  
Christian R. Nelson ◽  
Charles L. Asbury ◽  
Sue Biggins
Keyword(s):  
Error Correction ◽  
Genetic Interactions ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Additional Mechanism ◽  
Microtubule Binding ◽  
Dividing Cells ◽  
Intrinsic Error

AbstractDividing cells detect and correct erroneous kinetochore-microtubule attachments during mitosis, thereby avoiding chromosome mis-segregation. Most studies of this process have focused on the Aurora B kinase, which phosphorylates microtubule-binding elements specifically at incorrectly attached kinetochores, promoting their release and providing another chance for proper attachments to form. However, growing evidence suggests additional mechanisms, potentially involving Mps1 kinase, that also underlie error correction. Because these mechanisms overlap in vivo, and because both Mps1 and Aurora B function in numerous other vital processes, their contributions to the correction of erroneous kinetochore attachments have been difficult to disentangle. Here we directly examine how Mps1 activity affects kinetochore-microtubule attachments using a reconstitution-based approach that allowed us to separate its effects from Aurora B activity. When endogenous Mps1 that co-purifies with isolated kinetochores is activated in vitro, it weakens their attachments to microtubules via phosphorylation of Ndc80, a major microtubule-binding element of the outer kinetochore. Mps1 phosphorylation of Ndc80 appears to contribute to error correction because phospho-deficient Ndc80 mutants exhibit genetic interactions and segregation defects when combined with mutants in an intrinsic error correction pathway. In addition, Mps1 phosphorylation of Ndc80 is stimulated on kinetochores lacking tension. These data suggest that Mps1 provides an additional mechanism for correcting erroneous kinetochore-microtubule attachments, complementing the well-known activity of Aurora B.

scholarly journals Aurora B phosphorylates Bub1 to promote spindle assembly checkpoint signaling

2021 ◽  
Author(s):  
Babhrubahan Roy ◽  
Simon J. Y. Han ◽  
Adrienne N. Fontan ◽  
Ajit P. Joglekar
Keyword(s):  
Error Correction ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Mitotic Checkpoint ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Checkpoint Signaling ◽  
Binding Interface ◽  
Anaphase Onset ◽  
Error Correction Mechanism

SummaryAccurate chromosome segregation during cell division requires amphitelic attachment of each chromosome to the spindle apparatus. This is ensured by the Spindle Assembly Checkpoint (SAC) [1], which delays anaphase onset in response to unattached chromosomes, and an error correction mechanism, which eliminates syntelic chromosome attachments [2]. The SAC is activated by the Mps1 kinase. Mps1 sequentially phosphorylates the kinetochore protein Spc105/KNL1 to license the recruitment of several signaling proteins including Bub1. These proteins produce the Mitotic Checkpoint Complex (MCC), which delays anaphase onset [3-8]. The error correction mechanism is regulated by the Aurora B kinase, which phosphorylates the microtubule-binding interface of the kinetochore. Aurora B is also known to promote SAC signaling indirectly [9-12]. Here we present evidence that Aurora B kinase activity directly promotes MCC production in budding yeast and human cells. Using the ectopic SAC activation (eSAC) system, we find that the conditional dimerization of Aurora B (or an Aurora B recruitment domain) with either Bub1 or Mad1, but not the ‘MELT’ motifs in Spc105/KNL1, leads to a SAC-mediated mitotic arrest [13-16]. Importantly, ectopic MCC production driven by Aurora B requires the ability of Bub1 to bind both Mad1 and Cdc20. These and other data show that Aurora B cooperates with Bub1 to promote MCC production only after Mps1 licenses Bub1 recruitment to the kinetochore. This direct involvement of Aurora B in SAC signaling is likely important for syntelically attached sister kinetochores that must delay anaphase onset in spite of reduced Mps1 activity due to their end-on microtubule attachment.

scholarly journals Chromosome bi-orientation on the mitotic spindle

2005 ◽  
Vol 360 (1455) ◽  
pp. 581-589 ◽  
Author(s):  
Tomoyuki U Tanaka
Keyword(s):  
Protein Kinase ◽  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Budding Yeast ◽  
Aurora B ◽  
Cohesin Complex ◽  
Spindle Poles ◽  
Anaphase Onset ◽  
Sister Kinetochore ◽  
Dependent Mechanism

For proper chromosome segregation, sister kinetochores must attach to microtubules extending from opposite spindle poles prior to anaphase onset. This state is called sister kinetochore bi-orientation or chromosome bi-orientation. The mechanism ensuring chromosome bi-orientation lies at the heart of chromosome segregation, but is still poorly understood. Recent evidence suggests that mal-oriented kinetochore-to-pole connections are corrected in a tension-dependent mechanism. The cohesin complex and the Ipl1/Aurora B protein kinase seem to be key regulators for this correction. In this article, I discuss how cells ensure sister kinetochore bi-orientation for all chromosomes, mainly focusing on our recent findings in budding yeast.

scholarly journals Tension promotes kinetochore-microtubule release in response to Aurora B activity

2020 ◽  
Author(s):  
Geng-Yuan Chen ◽  
Fioranna Renda ◽  
Huaiying Zhang ◽  
Alper Gokden ◽  
Daniel Z. Wu ◽  
...  
Keyword(s):  
Cell Division ◽  
Error Correction ◽  
Chromosome Segregation ◽  
Kinase Activity ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Spindle Poles ◽  
Low Tension

AbstractAurora B kinase regulates kinetochore-microtubule interactions to ensure accurate chromosome segregation in cell division. Tension provides a signal to discriminate attachment errors from bi-oriented kinetochores with sisters correctly attached to opposite spindle poles. Current models focus on tension as an input to locally regulate Aurora B activity. Here we show that the outcome of Aurora B activity depends on tension. Using an optogenetic approach to manipulate Aurora B at individual kinetochores, we find that kinase activity promotes microtubule release when tension is high. Conversely, when tension is low, Aurora B activity promotes depolymerization of kinetochore-microtubule bundles while maintaining attachment. We propose that tension is a signal inducing distinct error-correction mechanisms, with release or depolymerization advantageous for typical errors characterized by high or low tension, respectively.

scholarly journals Tension promotes kinetochore–microtubule release by Aurora B kinase

2021 ◽  
Vol 220 (6) ◽  
Author(s):  
Geng-Yuan Chen ◽  
Fioranna Renda ◽  
Huaiying Zhang ◽  
Alper Gokden ◽  
Daniel Z. Wu ◽  
...  
Keyword(s):  
Error Correction ◽  
Chromosome Segregation ◽  
Input Signal ◽  
Kinase Activity ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Catch Bond ◽  
Spindle Poles ◽  
Low Tension

To ensure accurate chromosome segregation, interactions between kinetochores and microtubules are regulated by a combination of mechanics and biochemistry. Tension provides a signal to discriminate attachment errors from bi-oriented kinetochores with sisters correctly attached to opposite spindle poles. Biochemically, Aurora B kinase phosphorylates kinetochores to destabilize interactions with microtubules. To link mechanics and biochemistry, current models regard tension as an input signal to locally regulate Aurora B activity. Here, we show that the outcome of kinetochore phosphorylation depends on tension. Using optogenetics to manipulate Aurora B at individual kinetochores, we find that kinase activity promotes microtubule release when tension is high. Conversely, when tension is low, Aurora B activity promotes depolymerization of kinetochore–microtubules while maintaining attachment. Thus, phosphorylation converts a catch-bond, in which tension stabilizes attachments, to a slip-bond, which releases microtubules under tension. We propose that tension is a signal inducing distinct error-correction pathways, with release or depolymerization being advantageous for typical errors characterized by high or low tension, respectively.

scholarly journals The Molecular Basis of Monopolin Recruitment to the Kinetochore

2018 ◽  
Author(s):  
Rebecca Plowman ◽  
Namit Singh ◽  
Angel Payan ◽  
Eris Duro ◽  
Kevin D. Corbett ◽  
...  
Keyword(s):  
Binding Sites ◽  
Molecular Basis ◽  
Budding Yeast ◽  
Binding Motif ◽  
Binding Motifs ◽  
Hydrophobic Cavity ◽  
Sister Kinetochore ◽  
Close Relatives ◽  
Yeast Meiosis ◽  
Meiosis I

AbstractIn budding yeast meiosis I, the kinetochores of each sister chromatid pair are fused by the monopolin complex to mediate their monoorientation on the meiosis I spindle, enabling the biorientation and segregation of homologs. Monopolin forms a V-shaped complex with binding sites for the kinetochore protein Dsn1 at the apices of the V, suggesting that monopolin forms a physical bridge between the two sister kinetochores. Here, we reveal the molecular basis of the monopolin-kinetochore interaction and identify the key interfaces required for monopolin function at the kinetochore. The disordered N-terminus of budding-yeast Dsn1 unexpectedly possesses two binding motifs for the monopolin subunit Csm1, encompassing the previously-identified “Box 1” and “Box 2-3” regions of Dsn1. Strikingly, Dsn1 Box 1 and Box 2-3 bind the same conserved hydrophobic cavity on the monopolin complex subunit Csm1, suggesting that they are mutually exclusive for Csm1 binding, yet both regions are critical for monopolin function in Saccharomyces cerevisiae meiosis I. We find that Dsn1 Box 1 is an ancestral monopolin-binding motif that is conserved throughout fungi, including in the fission yeast Schizosaccharomyces pombe. In contrast, Box 2-3 is found only in species with sequence-defined point centromeres (S. cerevisiae and its close relatives), suggesting that this region contributes specifically to sister kinetochore crosslinking in meiosis I. Finally, we propose that phosphorylation of two conserved serine residues in Box 3 may stabilize monopolin at the kinetochore, providing a potential mechanism for enforcing specific sister kinetochore crosslinking in meiosis I.

scholarly journals The Aurora B Kinase Promotes Inner and Outer Kinetochore Interactions in Budding Yeast

Genetics ◽  
2013 ◽  
Vol 194 (3) ◽  
pp. 785-789 ◽  
Author(s):  
Bungo Akiyoshi ◽  
Christian R. Nelson ◽  
Sue Biggins
Keyword(s):  
Budding Yeast ◽  
Aurora B ◽  
Aurora B Kinase
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