Microtubule Polymerization Dynamics

Desai, Arshad; Mitchison, Timothy J.

doi:10.1146/annurev.cellbio.13.1.83

Cited by 2,327 publications

(2,131 citation statements)

References 183 publications

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“…Within centrosomes, the -TuRC nucleates microtubules promoting polymerisation of and tubulin subunits; the formed microtubule prolifaments are then bundled together into the tubular microtubule fibre (Zheng et al, 1995;Moritz et al, 2000;Job et al, 2003;Desai and Mitchison, 1997;Nogales, 2000). Microtubule fibres are polar, the negative ends reside at centrosomes and the positive ends project outwards.…”

Section: Centrosome Sister Chromatidmentioning

confidence: 99%

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63

Smith¹,

Dejsuphong

Balestrini³

et al. 2009

Nat Cell Biol

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The effects of ATM and ATR signalling induced by chromosomal breakage have been described extensively in modulating cell cycle progression up to the onset of mitosis.However, DNA damage checkpoint responses in mitotic cells are not well understood.This thesis reports on the effects of double strand breaks on the progression of mitosis.We found ATM and ATR activation can occur in mitotic Xenopus laevis egg extract and the induction of ATM and ATR by chromosomal breakages inhibits spindle assembly in both Xenopus egg extract and somatic cells. The delay in mitotic progression induced by ATM and ATR was found not to involve major spindle assembly factors activities such as, Cdk1, Plx1 and RCC1/Ran-GTP. However, normal anastral spindles formation around linear DNA coated beads, which can activate ATM and ATR, linked centrosome-driven spindle assembly to ATM and ATR dependent spindle defects. cDNA expression library screening was undertaken to identify novel ATM and ATR targets in this mitotic checkpoint pathway, through which the novel centrosomal protein XCEP63 was identified as a likely candidate. Data obtained from depletion and reconstitution of XCEP63 in Xenopus egg extract established that normal centrosome-driven spindle assembly requires XCEP63. Moreover, ATM and ATR phosphorylates XCEP63 on serine 560 and promotes delocalisation from the centrosome. ATM and ATR inhibition or addition of non-phosphorylable XCEP63 recombinant protein mutated at serine 560 prevents spindle assembly abnormalities.These findings suggest that ATM and ATR regulate mitotic events by targeting XCEP63 and centrosome-dependent spindle assembly. This pathway may provide support for DNA repair processes or regulate cell survival in the presence of mitotic DNA damage. 3

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Section: Centrosome Sister Chromatidmentioning

confidence: 99%

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63

Smith¹,

Dejsuphong

Balestrini³

et al. 2009

Nat Cell Biol

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“…The percentage of time the microtubules spent in growing and shortening states were decreased by 60% and 46%, respectively, while the percentage of time the microtubules spent in pause state was increased by 137%. It has been believed that catastrophe (a transition from a growing or a pause state to a shortening state) and rescue (a transition from a shortening state to a growing or a pause state) frequencies play important roles in regulating microtubule dynamics [39,40]. The time based rescue frequency (events/min) was found to be increased by 50% and the catastrophe frequency (events/ min) was found to be decreased by 30% in the presence of 5 mM benomyl compared to the control cells.…”

Section: 3mentioning

confidence: 99%

Kinetic stabilization of microtubule dynamic instability by benomyl increases the nuclear transport of p53

Rathinasamy

Panda

2008

Biochemical Pharmacology

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“…This ability for being in an everlasting state of changing length as won microtubules the name of "searching devices" for specific targets in the cell [3,8]. A key property allowing for this bistable state is the dynamic instability [4]. Due to conformational asymmetry of the constituting microtubule subunit, the heterodimer α,β-tubulin, a microtubule has a polar structure and it grows at a plus-end and shrinks at its minus-end.…”

Section: Introductionmentioning

confidence: 99%

Collision induced spatial organization of microtubules

Baulin¹,

Marques²,

Thalmann³

2007

Biophysical Chemistry

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The dynamic behavior of microtubules in solution can be strongly modified by interactions with walls or other structures. We examine here a microtubule growth model where the increase in size of the plus-end is perturbed by collisions with other microtubules. We show that such a simple mechanism of constrained growth can induce ordered structures and patterns from an initially isotropic and homogeneous suspension. First, microtubules self-organize locally in randomly oriented domains that grow and compete with each other. By imposing even a weak orientation bias, external forces like gravity or cellular boundaries may bias the domain distribution eventually leading to a macroscopic sample orientation.

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Microtubule Polymerization Dynamics

Cited by 2,327 publications

References 183 publications

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63

Kinetic stabilization of microtubule dynamic instability by benomyl increases the nuclear transport of p53

Collision induced spatial organization of microtubules

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