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Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK

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) pred...

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Autores principales: Shrestha, Roshan L., Draviam, Viji M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748344/
https://www.ncbi.nlm.nih.gov/pubmed/23891108
http://dx.doi.org/10.1016/j.cub.2013.06.040
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author Shrestha, Roshan L.
Draviam, Viji M.
author_facet Shrestha, Roshan L.
Draviam, Viji M.
author_sort Shrestha, Roshan L.
collection PubMed
description 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.
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spelling pubmed-37483442013-08-21 Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK Shrestha, Roshan L. Draviam, Viji M. Curr Biol Article 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. Cell Press 2013-08-19 /pmc/articles/PMC3748344/ /pubmed/23891108 http://dx.doi.org/10.1016/j.cub.2013.06.040 Text en © 2013 The Authors https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Article
Shrestha, Roshan L.
Draviam, Viji M.
Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK
title Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK
title_full Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK
title_fullStr Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK
title_full_unstemmed Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK
title_short Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK
title_sort lateral to end-on conversion of chromosome-microtubule attachment requires kinesins cenp-e and mcak
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748344/
https://www.ncbi.nlm.nih.gov/pubmed/23891108
http://dx.doi.org/10.1016/j.cub.2013.06.040
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