Pericentric Chromatin Is Organized into an Intramolecular Loop in Mitosis

Yeh, Elaine; Haase, Julian; Paliulis, Leocadia V.; Joglekar, Ajit P.; Bond, Lisa M.; Bouck, David C.; Salmon, Edward D.; Bloom, Kerry

doi:10.1016/j.cub.2007.12.019

Cited by 143 publications

(257 citation statements)

References 40 publications

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“…However, similar to other eukaryotes, cohesin is enriched within a 20-to 50-kb domain around centromeres (Blat and Kleckner 1999;Glynn et al 2004;Weber et al 2004). Strikingly, the pericentric cohesins in budding yeast appear to be arranged as a cyclindrical array around the spindle (Yeh et al 2008), which may be due to the formation of an intramolecular C loop on each sister chromatid that extends 25 kb (Yeh et al 2008). Cohesin would therefore encircle a single chromatid rather than sisters in this region, resolving the apparent "cohesin" paradox where the highest levels of cohesin reside in the areas that are physically split at metaphase.…”

Section: The Centromerementioning

confidence: 83%

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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Section: The Centromerementioning

confidence: 83%

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

2013

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“…A recent immunoelectron microscopy study confirmed that CENP-A occupies the outer third of the centromeric chromatin (13). An alternative looping model has been suggested for the point centromere of budding yeast (14).…”

mentioning

confidence: 93%

A super-resolution map of the vertebrate kinetochore

Ribeiro

Vagnarelli

Yang

et al. 2010

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

192

217

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A longstanding question in centromere biology has been the organization of CENP-A-containing chromatin and its implications for kinetochore assembly. Here, we have combined genetic manipulations with deconvolution and super-resolution fluorescence microscopy for a detailed structural analysis of chicken kinetochores. Using fluorescence microscopy with subdiffraction spatial resolution and single molecule sensitivity to map protein localization in kinetochore chromatin unfolded by exposure to a low salt buffer, we observed robust amounts of H3K9me3, but only low levels of H3K4me2, between CENP-A subdomains in unfolded interphase prekinetochores. Constitutive centromere-associated network proteins CENP-C and CENP-H localize within CENP-A-rich subdomains (presumably on H3-containing nucleosomes) whereas CENP-T localizes in interspersed H3-rich blocks. Although interphase prekinetochores are relatively more resistant to unfolding than surrounding pericentromeric heterochromatin, mitotic kinetochores are significantly more stable, reflecting mitotic kinetochore maturation. Loss of CENP-H, CENP-N, or CENP-W had little or no effect on the unfolding of mitotic kinetochores. However, loss of CENP-C caused mitotic kinetochores to unfold to the same extent as their interphase counterparts. Based on our results we propose a new model for inner centromeric chromatin architecture in which chromatin is folded as a layered boustrophedon, with planar sinusoids containing interspersed CENP-A-rich and H3-rich subdomains oriented toward the outer kinetochore. In mitosis, a CENP-C-dependent mechanism crosslinks CENP-A blocks of different layers together, conferring extra stability to the kinetochore.

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Section: Introductionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

Condensin Regulates the Stiffness of Vertebrate Centromeres

Ribeiro

Gatlin

Yang

et al. 2009

MBoC

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137

147

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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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Pericentric Chromatin Is Organized into an Intramolecular Loop in Mitosis

Abstract: The C loop conformation reveals the structural basis for sister-kinetochore clustering in budding yeast and for kinetochore biorientation and thus resolves the paradox of maximal interstrand separation in regions of highest cohesin concentration.

Cited by 143 publications

References 40 publications

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

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

A super-resolution map of the vertebrate kinetochore

Condensin Regulates the Stiffness of Vertebrate Centromeres

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