Building an integrated model of chromosome congression

Auckland, Philip; McAinsh, Andrew D.

doi:10.1242/jcs.169367

Cited by 35 publications

(40 citation statements)

References 128 publications

(188 reference statements)

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“…HeLaK cells, which are immortal, aneuploid tumor cells with a high proliferation capacity might therefore be strongly affected in mitotic processes. Although we were not able to identify the original cause of the observed chromosome congression defect (reviewed in Auckland & McAinsh, 2015), it is possible that global metabolic alterations or the deregulation of a combination of factors involved in chromosome migratory mechanisms affect the cell's ability to properly align chromosomes at the spindle equator and synchronously pull them to the opposite poles. Accordingly, changes in transcriptional programs might be the driving parameter for the developmental defects observed in PWWP2A-depleted X. laevis and X. tropicalis embryos.…”

Section: Discussionmentioning

confidence: 96%

Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation

et al. 2017

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Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A is a functionally uncharacterized, vertebrate-specific protein that binds very tightly to chromatin through a concerted multivalent binding mode. Two internal protein regions mediate H2A.Z-specificity and nucleosome interaction, whereas the PWWP domain exhibits direct DNA binding. Genome-wide mapping reveals that PWWP2A binds selectively to H2A.Z-containing nucleosomes with strong preference for promoters of highly transcribed genes. In human cells, its depletion affects gene expression and impairs proliferation via a mitotic delay. While PWWP2A does not influence H2A.Z occupancy, the C-terminal tail of H2A.Z is one important mediator to recruit PWWP2A to chromatin. Knockdown of PWWP2A in results in severe cranial facial defects, arising from neural crest cell differentiation and migration problems. Thus, PWWP2A is a novel H2A.Z-specific multivalent chromatin binder providing a surprising link between H2A.Z, chromosome segregation, and organ development.

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Section: Discussionmentioning

confidence: 96%

Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation

et al. 2017

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“…Indeed, associations with dynamic microtubules contribute to multiple aspects of mitosis. For example, in addition to motor-driven chromosome congression, as discussed above, depolymerization-coupled pulling on kinetochores also contributes to chromosome congression and relies on the ability of the kinetochore to maintain its association with a depolymerizing microtubule (Auckland and McAinsh, 2015). Additionally, chromosomes undergo oscillations during metaphase (Jaqaman et al, 2010;Skibbens et al, 1993), thereby requiring one sister chromatid to associate with depolymerizing microtubules while the other sister chromatid associates with elongating microtubules.…”

Section: Dynamic Microtubule Tip Trackingmentioning

confidence: 99%

The kinetochore–microtubule interface at a glance

Monda

Cheeseman

2018

Journal of Cell Science

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Accurate chromosome segregation critically depends on the formation of attachments between microtubule polymers and each sister chromatid. The kinetochore is the macromolecular complex that assembles at the centromere of each chromosome during mitosis and serves as the link between the DNA and the microtubules. In this Cell Science at a Glance article and accompanying poster, we discuss the activities and molecular players that are involved in generating kinetochore-microtubule attachments, including the initial stages of lateral kinetochore-microtubule interactions and maturation to stabilized end-on attachments. We additionally explore the features that contribute to the ability of the kinetochore to track with dynamic microtubules. Finally, we examine the contributions of microtubule-associated proteins to the organization and stabilization of the mitotic spindle and the control of microtubule dynamics.

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“…Inserting the solution of Eqs. (8) and 9back into the energy functional (6), we obtain the effective potential V as a function of the tip height z 0 :…”

Section: Effective Potential Of Tip Curlingmentioning

confidence: 99%

“…This dynamical instability of MTs offers an efficient way for re-organization of lonh filaments, e.g. at the onset of mitosis 7,8 , and an important 'search-and-find' mechanism to explore the cellular space and capture less diffusible cargoes for subsequent transport 3,[9][10][11] . It is therefore important to fully understand the underlying physical mechanisms behind this dynamic instability.…”

Section: Introductionmentioning

confidence: 99%

Structural effects of cap, crack, and intrinsic curvature on the microtubule catastrophe kinetics

Lee

Terentjev

2019

The Journal of Chemical Physics

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Microtubules (MTs) experience an effect called “catastrophe,” which is the transition from the MT growth to a sudden dramatic shrinkage in length. The straight guanosine triphosphate (GTP)-tubulin cap at the filament tip and the intrinsic curvature of guanosine diphosphate (GDP)-tubulins are known to be the key thermodynamic factors that determine MT catastrophe, while the hydrolysis of this GTP-cap acts as the kinetic control of the process. Although several theoretical models have been developed, assuming the catastrophe occurs when the GTP-cap shrinks to a minimal stabilizing size, the structural effect of the GTP-cap and GDP-curvature is not explicitly included; thus, their influence on catastrophe kinetics remains less understood. To investigate this structural effect, we apply a single-protofilament model with one GTP-cap while assuming a random hydrolysis mechanism and take the occurrence of a crack in the lateral bonds between neighboring protofilaments as the onset of the catastrophe. Therein, we find the effective potential of the tip along the peel-off direction and formulate the catastrophe kinetics as a mean first-passage time problem, subject to thermal fluctuations. We consider cases with and without a compressive force on the MT tip, both of which give a quadratic effective potential, making MT catastrophe an Ornstein-Uhlenbeck process in our formalism. In the free-standing case, the mean catastrophe time has a sensitive tubulin-concentration dependence, similar to a double-exponential function, and agrees well with the experiment. For a compressed MT, we find a modified exponential function of force that shortens the catastrophe time.

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Building an integrated model of chromosome congression

Cited by 35 publications

References 128 publications

Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation

Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation

The kinetochore–microtubule interface at a glance

Structural effects of cap, crack, and intrinsic curvature on the microtubule catastrophe kinetics

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