An Mtw1 Complex Promotes Kinetochore Biorientation that Is Monitored by the Ipl1/Aurora Protein Kinase

Pinsky, Benjamin A.; Tatsutani, Sean Y.; Collins, Kimberly A.; Biggins, Sue

doi:10.1016/s1534-5807(03)00322-8

Cited by 97 publications

(102 citation statements)

References 42 publications

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“…Overall, however, the data suggest improved kinetochore attachment in mtw1top2-SNM cells is not sufficient to restore chromosome segregation. This is similar to what has been documented in mtw1ipl1 mutants; one possibility is that even though mtw1 kinetochores are not being actively disconnected they are unable to remain attached to the spindle during anaphase (Pinsky et al, 2003).…”

Section: T H Warsi Et Alsupporting

confidence: 86%

DNA Topoisomerase II Is a Determinant of the Tensile Properties of Yeast Centromeric Chromatin and the Tension Checkpoint

Warsi

Navarro

Bachant

2008

MBoC

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Centromeric (CEN) chromatin is placed under mechanical tension and stretches as kinetochores biorient on the mitotic spindle. This deformation could conceivably provide a readout of biorientation to error correction mechanisms that monitor kinetochore-spindle interactions, but whether CEN chromatin acts in a tensiometer capacity is unresolved. Here, we report observations linking yeast Topoisomerase II (Top2) to both CEN mechanics and assessment of interkinetochore tension. First, in top2-4 and sumoylation-resistant top2-SNM mutants CEN chromatin stretches extensively during biorientation, resulting in increased sister kinetochore separation and preanaphase spindle extension. Our data indicate increased CEN stretching corresponds with alterations to CEN topology induced in response to tension. Second, Top2 potentiates aspects of the tension checkpoint. Mutations affecting the Mtw1 kinetochore protein activate Ipl1 kinase to detach kinetochores and induce spindle checkpoint arrest. In mtw1top2-4 and mtw1top2-SNM mutants, however, kinetochores are resistant to detachment and checkpoint arrest is attenuated. For top2-SNM cells, CEN stretching and checkpoint attenuation occur even in the absence of catenation linking sister chromatids. In sum, Top2 seems to play a novel role in CEN compaction that is distinct from decatenation. Perturbations to this function may allow weakened kinetochores to stretch CENs in a manner that mimics tension or evades Ipl1 surveillance. INTRODUCTIONAccurate chromosome segregation requires that sister kinetochores connect to microtubules from opposing poles of the mitotic spindle, a process known as biorientation. Misaligned kinetochore attachments can also occur, and they must be resolved to prevent lethal chromosome segregation errors or the formation of aneuploid cells. Syntelic attachments arise when sister kinetochores connect to microtubules from the same spindle pole; merotelic attachments result if a single kinetochore attaches to both poles. The Aurora-B kinases, complexed with conserved INCENP/ Sli15 and Survivin/Bir1 subunits of the chromosomal passenger complex, are key regulators of the error correction machinery that resolves such inappropriate attachments (reviewed in Ruchaud et al., 2007). Aurora-B (Ipl1 in budding yeast) facilitates error correction through two mechanisms. First, these kinases destabilize defective kinetochore-microtubule interactions by phosphorylating kinetochore-associated proteins. Second, Ipl1/Aurora-B plays a role in activating the spindle assembly checkpoint (SAC), both in response to syntelic attachments as well as mutations that affect the kinetochore or sister chromatid cohesion. Checkpoint activation may occur indirectly because Ipl1/Aurora-B creates unoccupied kinetochores (Pinsky et al., 2006) or directly through phosphorylation of SAC regulators (King et al., 2007).The manner in which Ipl1/Aurora-B distinguishes such a wide range of spindle lesions is not well understood. With the exception of merotelic interactions (Cimini, 2007), those att...

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Section: T H Warsi Et Alsupporting

confidence: 86%

DNA Topoisomerase II Is a Determinant of the Tensile Properties of Yeast Centromeric Chromatin and the Tension Checkpoint

Warsi

Navarro

Bachant

2008

MBoC

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“…reduced Ipl1 activity restores defective kinetochoremicrotubule interactions (Biggins & Murray 2001;Pinsky et al 2003). In summary, the Ipl1-Sli15 complex facilitates bi-orientation by promoting reorientation of kinetochore-spindle pole connections in a tension-dependent manner (figure 4).…”

Section: Roles Of the Ipl1-sli15 (Aurora B-incenp) Kinase Complex In mentioning

confidence: 97%

Chromosome bi-orientation on the mitotic spindle

Tanaka

2005

Phil. Trans. R. Soc. B

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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.

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“…The Mis12 (composed of Mtw1, Dsn1, Nnf1, and Nsl1 at a 1:1:1:1 stoichiometry (Euskirchen 2002;De Wulf et al 2003;Nekrasov et al 2003;Pinsky et al 2003;Westermann et al 2003;Maskell et al 2010;Hornung et al 2011), Spc105 (composed of Spc105 and Ydr532/Kre28 at a 1:2 Spc105:Kre28 ratio (Nekrasov et al 2003;Pagliuca et al 2009) and Ndc80 (composed of a 1:1:1:1 ratio of Ndc80, Nuf2, Spc24, and Spc25 (Janke et al 2001;Wigge and Kilmartin 2001;Ciferri et al 2005;Wei et al 2005) . Consistent with this, yeast mutants in KMN fail to make kinetochore-microtubule attachments (Wigge et al 1998;Nekrasov et al 2003;Pinsky et al 2006;Pagliuca et al 2009).…”

Section: Kmnmentioning

confidence: 99%

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

2013

Self Cite

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The propagation of all organisms depends on the accurate and orderly segregation of chromosomes in mitosis and meiosis. Budding yeast has long served as an outstanding model organism to identify the components and underlying mechanisms that regulate chromosome segregation. This review focuses on the kinetochore, the macromolecular protein complex that assembles on centromeric chromatin and maintains persistent load-bearing attachments to the dynamic tips of spindle microtubules. The kinetochore also serves as a regulatory hub for the spindle checkpoint, ensuring that cell cycle progression is coupled to the achievement of proper microtubule-kinetochore attachments. Progress in understanding the composition and overall architecture of the kinetochore, as well as its properties in making and regulating microtubule attachments and the spindle checkpoint, is discussed. TABLE OF CONTENTS Abstract 817Introduction 818

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An Mtw1 Complex Promotes Kinetochore Biorientation that Is Monitored by the Ipl1/Aurora Protein Kinase

Cited by 97 publications

References 42 publications

DNA Topoisomerase II Is a Determinant of the Tensile Properties of Yeast Centromeric Chromatin and the Tension Checkpoint

DNA Topoisomerase II Is a Determinant of the Tensile Properties of Yeast Centromeric Chromatin and the Tension Checkpoint

Chromosome bi-orientation on the mitotic spindle

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

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