The Condensin I Subunit Barren/CAP-H Is Essential for the Structural Integrity of Centromeric Heterochromatin during Mitosis

Oliveira, Raquel; Coelho, Paula A.; Sunkel, Cláudio E.

doi:10.1128/mcb.25.20.8971-8984.2005

Cited by 100 publications

(126 citation statements)

References 51 publications

(50 reference statements)

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“…We could not confirm results reported for Drosophila, in which similar kinetochore movements were observed, but where the distortions of the centromeric chromatin were irreversible (Oliveira et al, 2005).…”

Section: Discussioncontrasting

confidence: 56%

“…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).…”

Section: Introductionmentioning

confidence: 98%

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Condensin Regulates the Stiffness of Vertebrate Centromeres

Ribeiro

Gatlin

Yang

et al. 2009

MBoC

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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Section: Discussioncontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 98%

Condensin Regulates the Stiffness of Vertebrate Centromeres

Ribeiro

Gatlin

Yang

et al. 2009

MBoC

137

147

View full text Add to dashboard Cite

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“…Yeast contains only condensin II. In Drosophila, condensin I has been reported to dominate mitotic chromosome condensation and to be necessary for stability of chromosomes during mitosis (Oliveira et al 2005). It is loaded onto chromosomes in early prophase, and remains highly dynamic throughout mitosis, undergoing bindingYunbinding turnover on a timescale of a few minutes (Oliveira et al 2007).…”

Section: Topoisomerase IImentioning

confidence: 99%

Micromechanical studies of mitotic chromosomes

2008

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Mitotic chromosomes respond elastically to forces in the nanonewton range, a property important to transduction of stresses used as mechanical regulatory signals during cell division. In addition to being important biologically, chromosome elasticity can be used as a tool for investigating the folding of chromatin. This paper reviews experiments studying stretching and bending stiffness of mitotic chromosomes, plus experiments where changes in chromosome elasticity resulting from chemical and enzyme treatments were used to analyse connectivity of chromatin inside chromosomes. Experiments with nucleases indicate that non-DNA elements constraining mitotic chromatin must be isolated from one another, leading to the conclusion that mitotic chromosomes have a chromatin Fnetwork_ or Fgel_ organization, with stretches of chromatin strung between Fcrosslinking_ points. The as-yet unresolved questions of the identities of the putative chromatin crosslinkers and their organization inside mitotic chromosomes are discussed.

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“…Condensin can reconfigure DNA topology in a Topo II-dependent manner (Stray et al, 2005) and has been suggested to localize to yeast CENs (Bachellier-Bassi et al, 2008). Condensin has also been implicated in preventing CEN expansion under tension (Oliveira et al, 2005;Gerlich et al, 2006;Yong-Gonzalez et al, 2007).…”

Section: Top2 Function In Cen Tensioningmentioning

confidence: 99%

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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The Condensin I Subunit Barren/CAP-H Is Essential for the Structural Integrity of Centromeric Heterochromatin during Mitosis

Cited by 100 publications

References 51 publications

Condensin Regulates the Stiffness of Vertebrate Centromeres

Condensin Regulates the Stiffness of Vertebrate Centromeres

Micromechanical studies of mitotic chromosomes

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

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