Tension-dependent Regulation of Microtubule Dynamics at Kinetochores Can Explain Metaphase Congression in Yeast

Gardner, Melissa K.; Pearson, Chad G.; Sprague, Brian L.; R., Zarzar, Ted; Bloom, Kerry; Salmon, Edward D.; Odde, David J.

doi:10.1091/mbc.e05-04-0275

Cited by 123 publications

(208 citation statements)

References 53 publications

(84 reference statements)

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“…Spatial cues such as polar ejection, length-dependent rates, and chemical gradients could rectify these issues (7, 34, 38-40, 42, 43). These cues could be included in our model to study phenomena such as oscillations in monopolar spindles and congression (35,39,42,43).…”

Section: Discussionmentioning

confidence: 99%

Minimal model for collective kinetochore–microtubule dynamics

Banigan

Chiou

Ballister

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Chromosome segregation during cell division depends on interactions of kinetochores with dynamic microtubules (MTs). In many eukaryotes, each kinetochore binds multiple MTs, but the collective behavior of these coupled MTs is not well understood. We present a minimal model for collective kinetochore–MT dynamics, based on in vitro measurements of individual MTs and their dependence on force and kinetochore phosphorylation by Aurora B kinase. For a system of multiple MTs connected to the same kinetochore, the force–velocity relation has a bistable regime with two possible steady-state velocities: rapid shortening or slow growth. Bistability, combined with the difference between the growing and shrinking speeds, leads to center-of-mass and breathing oscillations in bioriented sister kinetochore pairs. Kinetochore phosphorylation shifts the bistable region to higher tensions, so that only the rapidly shortening state is stable at low tension. Thus, phosphorylation leads to error correction for kinetochores that are not under tension. We challenged the model with new experiments, using chemically induced dimerization to enhance Aurora B activity at metaphase kinetochores. The model suggests that the experimentally observed disordering of the metaphase plate occurs because phosphorylation increases kinetochore speeds by biasing MTs to shrink. Our minimal model qualitatively captures certain characteristic features of kinetochore dynamics, illustrates how biochemical signals such as phosphorylation may regulate the dynamics, and provides a theoretical framework for understanding other factors that control the dynamics in vivo.

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Section: Discussionmentioning

confidence: 99%

Minimal model for collective kinetochore–microtubule dynamics

Banigan

Chiou

Ballister

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, tension prolongs the lifetime of kinetochore-microtubule interactions in vitro, suggesting that tension directly stabilizes microtubule attachments (Franck et al 2007;Akiyoshi et al 2010). Elegant computer modeling supports the role of tension in stabilizing attachments (Gardner et al 2005).…”

Section: Establishing Kinetochore Biorientationmentioning

confidence: 79%

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

2013

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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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“…However, such an interpretation would be misleading. Indeed, many studies over the years have shown that tension can stabilize MT attachment to kinetochores and promote MT growth (Nicklas and Koch, 1969;Rieder and Salmon, 1994;Inoue and Salmon, 1995;Skibbens et al, 1995;Nicklas et al, 2001;Gardner et al, 2005;Figure 6, e and f).…”

Section: Mitotic Delay In Condensin-depleted Cells Is Caused By Prolomentioning

confidence: 99%

Condensin Regulates the Stiffness of Vertebrate Centromeres

Ribeiro

Gatlin

Yang

et al. 2009

MBoC

134

142

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When chromosomes are aligned and bioriented at metaphase, the elastic stretch of centromeric chromatin opposes pulling forces exerted on sister kinetochores by the mitotic spindle. Here we show that condensin ATPase activity is an important regulator of centromere stiffness and function. Condensin depletion decreases the stiffness of centromeric chromatin by 50% when pulling forces are applied to kinetochores. However, condensin is dispensable for the normal level of compaction (rest length) of centromeres, which probably depends on other factors that control higher-order chromatin folding. Kinetochores also do not require condensin for their structure or motility. Loss of stiffness caused by condensindepletion produces abnormal uncoordinated sister kinetochore movements, leads to an increase in Mad2(؉) kinetochores near the metaphase plate and delays anaphase onset. INTRODUCTIONCentromeric chromatin is a special region of chromosomes that has important mechanical and signaling functions in mitosis (Pidoux and Allshire, 2005;Ekwall, 2007;Cheeseman and Desai, 2008;Vagnarelli et al., 2008). In metaphase, pulling forces generated by interactions between spindle microtubules (MTs) and kinetochores are opposed by tension produced by centromeric chromatin stretch. Centromere and kinetochore tension and stretch are important for maintaining chromosome alignment (McIntosh et al., 2002), stabilizing kinetochore microtubule (kMT) attachments (Nicklas and Koch, 1969), spindle checkpoint signaling (Musacchio and Salmon, 2007;McEwen and Dong, 2009), and also for the back-to-back orientation of sister kinetochores (Loncarek et al., 2007). At least three independent factors have roles in the establishment of centromeric tension in metaphase: sister chromatid cohesion (Yeh et al., 2008), the elastic properties of chromatin (Houchmandzadeh et al., 1997;Almagro et al., 2004;Marko, 2008), and the higher order structure of the centromeric chromatin.Condensin is important for the architecture of mitotic chromosome arms (Coelho et al., 2003;Hudson et al., 2003;Hirota et al., 2004;Hirano, 2006), but it also localizes to centromeres (Saitoh et al., 1994;Gerlich et al., 2006), where condensin I, but not condensin II was reported to have a role in stabilizing the structure (Gerlich et al., 2006). It has recently been suggested that condensin could have a role in regulating the elastic behavior of centromeric chromatin. One study found that condensin I-depleted Drosophila chromosomes were unable to align at a metaphase plate, had distorted kinetochore structures, and lost elasticity of their centromeric chromatin (Oliveira et al., 2005). However a similar study in human cells reported that although loss of condensin I caused kinetochores to undergo abnormal movements, these movements were bidirectional (e.g., reversible; Gerlich et al., 2006).Even after the publication of those results, the regulation and functional significance of centromere stretch remained unknown. An elegant study in budding yeast went on to find that chromatin struct...

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Tension-dependent Regulation of Microtubule Dynamics at Kinetochores Can Explain Metaphase Congression in Yeast

Cited by 123 publications

References 53 publications

Minimal model for collective kinetochore–microtubule dynamics

Minimal model for collective kinetochore–microtubule dynamics

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

Condensin Regulates the Stiffness of Vertebrate Centromeres

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