Force Transduction by the Microtubule-Bound Dam1 Ring

Armond, Jonathan W.; Turner, Matthew S.

doi:10.1016/j.bpj.2010.01.004

Cited by 14 publications

(12 citation statements)

References 42 publications

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“…In later versions of these models, the splaying tendency of GDP tubulin protofilaments to curve in this manner provides a “power stroke” that pulls on centromeric chromatin through kinetochore fibrils [7]. Other models utilize ring-like coupling kinetochore Dam1/DASH complexes for this coupling [8–11]. …”

Section: Introductionmentioning

confidence: 99%

Electrostatic forces drive poleward chromosome motions at kinetochores

Gagliardi

Shain

2016

Cell Div

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BackgroundRecent experiments regarding Ndc80/Hec1 in force generation at kinetochores for chromosome motions have prompted speculation about possible models for interactions between positively charged molecules at kinetochores and negative charge at and near the plus ends of microtubules.DiscussionA clear picture of how kinetochores and centrosomes establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. The current paradigm of molecular cell biology requires that specific molecules, or molecular geometries, for force generation be identified. However, it is possible to explain several different mitotic motions—including poleward force production at kinetochores—within a classical electrostatics approach in terms of experimentally known charge distributions, modeled as surface and volume bound charges interacting over nanometer distances.ConclusionWe propose here that implicating Ndc80/Hec1 as a bound volume positive charge distribution in electrostatic generation of poleward force at kinetochores is most consistent with a wide range of experimental observations on mitotic motions, including polar production of poleward force and chromosome congression.

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Section: Introductionmentioning

confidence: 99%

Electrostatic forces drive poleward chromosome motions at kinetochores

Gagliardi

Shain

2016

Cell Div

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“…Previous mathematical models of the kinetochore–MT binding site included specific structural features that limited the independence of MAP–MT interactions. 6,15,20,21,25,33,39 Lifting this restriction has a surprisingly large effect on the kinetics of MT attachment and this system’s thermodynamics. For example, in Hill’s sleeve model, the number of possible MT–MAPs binding configuration is only 65, which is equal to the number of MAPs in the sleeve.…”

Section: Resultsmentioning

confidence: 99%

“…Previous theoretical studies have modeled the kinetochore as containing the distinct MT-binding sites, each composed of multiple MT-binding proteins arranged in a cylinder 20,21,39 or a ring 6,15,25,31 (reviewed in Grishchuk et al 18 ) (Fig. 1a).…”

Section: Introductionmentioning

confidence: 99%

Highly Transient Molecular Interactions Underlie the Stability of Kinetochore–Microtubule Attachment During Cell Division

2013

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Chromosome segregation during mitosis is mediated by spindle microtubules that attach to chromosomal kinetochores with strong yet labile links. The exact molecular composition of the kinetochore–microtubule interface is not known but microtubules are thought to bind to kinetochores via the specialized microtubule-binding sites, which contain multiple microtubule-binding proteins. During prometaphase the lifetime of microtubule attachments is short but in metaphase it increases 3-fold, presumably owing to dephosphorylation of the microtubule-binding proteins that increases their affinity. Here, we use mathematical modeling to examine in quantitative and systematic manner the general relationships between the molecular properties of microtubule-binding proteins and the resulting stability of microtubule attachment to the protein-containing kinetochore site. We show that when the protein connections are stochastic, the physiological rate of microtubule turnover is achieved only if these molecular interactions are very transient, each lasting fraction of a second. This “microscopic” time is almost four orders of magnitude shorter than the characteristic time of kinetochore–microtubule attachment. Cooperativity of the microtubule-binding events further increases the disparity of these time scales. Furthermore, for all values of kinetic parameters the microtubule stability is very sensitive to the minor changes in the molecular constants. Such sensitivity of the lifetime of microtubule attachment to the kinetics and cooperativity of molecular interactions at the microtubule-binding site may hinder the accurate regulation of kinetochore–microtubule stability during mitotic progression, and it necessitates detailed experimental examination of the microtubule-binding properties of kinetochore-localized proteins.

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“…The most valuable studies would examine how measurable quantities – such as attachment lifetimes and speeds versus load force, or distributions of rupture force at fixed loading rates – vary as model parameters are adjusted over their full plausible ranges. (As an example, see [61]. )…”

Section: The Case Is Not Closedmentioning

confidence: 99%

Kinetochores’ gripping feat: conformational wave or biased diffusion?

Asbury¹,

Tien²,

Davis³

2011

Trends in Cell Biology

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Climbing up a cliff while the rope unravels underneath your fingers does not sound like a well planned adventure. Yet chromosomes face a similar challenge during each cell division. Their alignment and accurate segregation depends on staying attached to the assembling and disassembling tips of microtubule fibers. This coupling is mediated by kinetochores, intricate machines that attach chromosomes to an ever changing microtubule substrate. Two models for kinetochore-microtubule coupling were proposed a quarter century ago: conformational wave and biased diffusion. These two models differ in their predictions for how coupling is performed and therefore in how the coupling can be regulated. The availability of purified kinetochore proteins has enabled a series of biochemical and biophysical analyses of the kinetochore-microtubule interface. Here, we discuss what these studies reveal about the contributions of each model.

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Force Transduction by the Microtubule-Bound Dam1 Ring

Cited by 14 publications

References 42 publications

Electrostatic forces drive poleward chromosome motions at kinetochores

Electrostatic forces drive poleward chromosome motions at kinetochores

Highly Transient Molecular Interactions Underlie the Stability of Kinetochore–Microtubule Attachment During Cell Division

Kinetochores’ gripping feat: conformational wave or biased diffusion?

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