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Curr Biol. 2013 Aug 19;23(16):1514-26. doi: 10.1016/j.cub.2013.06.040. Epub 2013 Jul 25.

Lateral to end-on conversion of chromosome-microtubule attachment requires kinesins CENP-E and MCAK.

Author information

1
Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK.

Erratum in

  • Curr Biol. 2013 Dec 2;23(23):2440-1.

Abstract

BACKGROUND:

Proper attachment of chromosomes to microtubules is crucial for the accurate segregation of chromosomes. Human chromosomes attach initially to lateral walls of microtubules. Subsequently, attachments to lateral walls disappear and attachments to microtubule ends (end-on attachments) predominate. While it is known in yeasts that lateral to end-on conversion of attachments occurs through a multistep process, equivalent conversion steps in humans remain unknown.

RESULTS:

By developing a high-resolution imaging assay to visualize intermediary steps of the lateral to end-on conversion process, we show that the mechanisms that bring a laterally bound chromosome and its microtubule end closer to each other are indispensable for proper end-on attachment because laterally attached chromosomes seldom detach. We show that end-on conversion requires (1) the plus-end-directed motor CENP-E to tether the lateral kinetochore onto microtubule walls and (2) the microtubule depolymerizer MCAK to release laterally attached microtubules after a partial end-on attachment is formed.

CONCLUSIONS:

By uncovering a CENP-E mediated wall-tethering event and a MCAK-mediated wall-removing event, we establish that human chromosome-microtubule attachment is achieved through a set of deterministic sequential events rather than stochastic direct capture of microtubule ends.

PMID:
23891108
PMCID:
PMC3748344
DOI:
10.1016/j.cub.2013.06.040
[Indexed for MEDLINE]
Free PMC Article

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