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 EB1 enables spindle microtubules to regulate centromeric recruitment of Aurora B

2014 ◽  
Vol 204 (6) ◽  
pp. 947-963 ◽  
Author(s):  
Budhaditya Banerjee ◽  
Cortney A. Kestner ◽  
P. Todd Stukenberg
Keyword(s):  
Mitotic Chromosome ◽  
Histone H3 ◽  
Aurora B ◽  
Dependent Manner ◽  
Histone H2a ◽  
Aurora B Kinase ◽  
Chromosomal Passenger Complex ◽  
Checkpoint Signaling ◽  
Chromosomal Passenger ◽  
Spindle Microtubules

The Aurora B kinase coordinates kinetochore–microtubule attachments with spindle checkpoint signaling on each mitotic chromosome. We find that EB1, a microtubule plus end–tracking protein, is required to enrich Aurora B at inner centromeres in a microtubule-dependent manner. This regulates phosphorylation of both kinetochore and chromatin substrates. EB1 regulates the histone phosphorylation marks (histone H2A phospho-Thr120 and histone H3 phospho-Thr3) that localize Aurora B. The chromosomal passenger complex containing Aurora B can be found on a subset of spindle microtubules that exist near prometaphase kinetochores, known as preformed K-fibers (kinetochore fibers). Our data suggest that EB1 enables the spindle microtubules to regulate the phosphorylation of kinetochores through recruitment of the Aurora B kinase.

scholarly journals Cdt1 modulates kinetochore-microtubule attachment stabilization via an Aurora B kinase-dependent mechanism

2017 ◽  
Author(s):  
Shivangi Agarwal ◽  
Kyle Paul Smith ◽  
Yizhuo Zhou ◽  
Aussie Suzuki ◽  
Richard J. McKenney ◽  
...  
Keyword(s):  
Aurora B ◽  
Deletion Mapping ◽  
Dependent Manner ◽  
Mitotic Progression ◽  
Aurora B Kinase ◽  
Winged Helix ◽  
Mitotic Kinase ◽  
Cellular Expression ◽  
Ndc80 Complex ◽  
Dna Replication Origin

AbstractRobust kinetochore-microtubule (kMT) attachment is critical for accurate chromosome segregation. G2/M-specific depletion of human Cdt1 that localizes to kinetochores in an Ndc80 complex-dependent manner, leads to abnormal kMT attachments and mitotic arrest. This indicates an independent mitotic role for Cdt1 in addition to its prototypic function in DNA replication origin licensing. Here, we show that Cdt1 directly binds to microtubules (MTs). Endogenous or transiently expressed Cdt1 localizes to both mitotic spindle MTs and kinetochores. Deletion mapping of Cdt1 revealed that the regions comprising the middle and C-terminal winged-helix domains but lacking the N-terminal unstructured region was required for efficient MT-binding. Mitotic kinase Aurora B interacts with and phosphorylates Cdt1. Aurora B-phosphomimetic Cdt1 exhibited attenuated MT-binding and its cellular expression induced defective kMT attachments with a concomitant delay in mitotic progression. Thus we provide mechanistic insight into how Cdt1 affects overall kMT stability in an Aurora B kinase phosphorylation-dependent manner; which is envisioned to augment the MT-binding of the Ndc80 complex.eTOC summary• Cdt1 binds to microtubules• The middle and the C-terminal winged-helix domains of Cdt1 are involved in MT-binding• Aurora B Kinase phosphorylates Cdt1 and influences its MT-binding• Aurora B-mediated Cdt1 phosphorylation is necessary for kMT stability and mitotic progression

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 SET/TAF1 forms a distance-dependent feedback loop with Aurora B and Bub1 as a tension sensor at centromeres

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yuichiro Asai ◽  
Rieko Matsumura ◽  
Yurina Hasumi ◽  
Hiroaki Susumu ◽  
Kyosuke Nagata ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Feedback Loop ◽  
Kinase Activity ◽  
Molecular Entity ◽  
Aurora B ◽  
Dependent Manner ◽  
Aurora B Kinase ◽  
Positive Feedback Loop ◽  
Spatiotemporal Regulation ◽  
Tension Sensor

Abstract During mitosis, spatiotemporal regulation of phosphorylation at the kinetochore is essential for accurate chromosome alignment and proper chromosome segregation. Aurora B kinase phosphorylates kinetochore substrates to correct improper kinetochore-microtubule (KT-MT) attachments, whereas tension across the centromeres inactivates Aurora B kinase, and PP2A phosphatase dephosphorylates the kinetochore proteins to stabilize the attachments. However, the molecular entity of the tension sensing mechanism remains elusive. In a previous report, we showed that centromeric SET/TAF1 on Sgo2 up-regulates Aurora B kinase activity via PP2A inhibition in prometaphase. Here we show that Aurora B and Bub1 at the centromere/kinetochore regulate both kinase activities one another in an inter-kinetochore distance-dependent manner, indicating a positive feedback loop. We further show that the centromeric pool of SET on Sgo2 depends on Bub1 kinase activity, and the centromeric localization of SET decreases in a distance-dependent manner, thereby inactivating Aurora B in metaphase. Consistently, ectopic targeting of SET to the kinetochores during metaphase hyperactivates Aurora B via PP2A inhibition, and thereby rescues the feedback loop. Thus, we propose that SET, Aurora B and Bub1 form a distance-dependent positive feedback loop, which spatiotemporally may act as a tension sensor at centromeres.

scholarly journals Cdt1 stabilizes kinetochore–microtubule attachments via an Aurora B kinase–dependent mechanism

2018 ◽  
Vol 217 (10) ◽  
pp. 3446-3463 ◽  
Author(s):  
Shivangi Agarwal ◽  
Kyle Paul Smith ◽  
Yizhuo Zhou ◽  
Aussie Suzuki ◽  
Richard J. McKenney ◽  
...  
Keyword(s):  
Aurora B ◽  
Deletion Mapping ◽  
Dependent Manner ◽  
Aurora B Kinase ◽  
Mitotic Kinase ◽  
Cellular Expression ◽  
Origin Licensing ◽  
Ndc80 Complex ◽  
Dna Replication Origin ◽  
Kinase Phosphorylation

Robust kinetochore–microtubule (kMT) attachment is critical for accurate chromosome segregation. G2/M-specific depletion of human Cdt1 that localizes to kinetochores in an Ndc80 complex–dependent manner leads to abnormal kMT attachments and mitotic arrest. This indicates an independent mitotic role for Cdt1 in addition to its prototypic function in DNA replication origin licensing. Here, we show that Cdt1 directly binds to microtubules (MTs). Endogenous or transiently expressed Cdt1 localizes to both mitotic spindle MTs and kinetochores. Deletion mapping of Cdt1 revealed that the regions comprising the middle and C-terminal winged-helix domains but lacking the N-terminal unstructured region were required for efficient MT binding. Mitotic kinase Aurora B interacts with and phosphorylates Cdt1. Aurora B–phosphomimetic Cdt1 exhibited attenuated MT binding, and its cellular expression induced defective kMT attachments with a concomitant delay in mitotic progression. Thus we provide mechanistic insight into how Cdt1 affects overall kMT stability in an Aurora B kinase phosphorylation-dependent manner; which is envisioned to augment the MT-binding of the Ndc80 complex.

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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