Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation

Kinetochores assemble on centromeric DNA and present arrays of proteins that attach directly to the dynamic ends of microtubules. Kinetochore proteins coordinate at the microtubule interface through oligomerization, but how oligomerization contributes to kinetochore function has remained unclear. He...

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Main Authors:	Umbreit, Neil T., Miller, Matthew P., Tien, Jerry F., Cattin-Ortolá, Jérôme, Gui, Long, Lee, Kelly K., Biggins, Sue, Asbury, Charles L., Davis, Trisha N.
Format:	Online
Language:	English
Published:	2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197110/

id	pubmed-4197110
recordtype	oai_dc
spelling	pubmed-41971102015-03-19 Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation Umbreit, Neil T. Miller, Matthew P. Tien, Jerry F. Cattin-Ortolá, Jérôme Gui, Long Lee, Kelly K. Biggins, Sue Asbury, Charles L. Davis, Trisha N. Article Kinetochores assemble on centromeric DNA and present arrays of proteins that attach directly to the dynamic ends of microtubules. Kinetochore proteins coordinate at the microtubule interface through oligomerization, but how oligomerization contributes to kinetochore function has remained unclear. Here, using a combination of biophysical assays and live-cell imaging, we find that oligomerization of the Dam1 kinetochore complex is required for its ability to form microtubule attachments that are robust against tension in vitro and in vivo. An oligomerization-deficient Dam1 complex that retains wild-type microtubule binding activity is primarily defective in coupling to disassembling microtubule ends under mechanical loads applied by a laser trap in vitro. In cells, the oligomerization-deficient Dam1 complex is unable to support stable bipolar alignment of sister chromatids, indicating failure of kinetochore-microtubule attachments under tension. We propose that oligomerization is an essential and conserved feature of kinetochore components that is required for accurate chromosome segregation during mitosis. 2014-09-19 /pmc/articles/PMC4197110/ /pubmed/25236177 http://dx.doi.org/10.1038/ncomms5951 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Umbreit, Neil T. Miller, Matthew P. Tien, Jerry F. Cattin-Ortolá, Jérôme Gui, Long Lee, Kelly K. Biggins, Sue Asbury, Charles L. Davis, Trisha N.
spellingShingle	Umbreit, Neil T. Miller, Matthew P. Tien, Jerry F. Cattin-Ortolá, Jérôme Gui, Long Lee, Kelly K. Biggins, Sue Asbury, Charles L. Davis, Trisha N. Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation
author_facet	Umbreit, Neil T. Miller, Matthew P. Tien, Jerry F. Cattin-Ortolá, Jérôme Gui, Long Lee, Kelly K. Biggins, Sue Asbury, Charles L. Davis, Trisha N.
author_sort	Umbreit, Neil T.
title	Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation
title_short	Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation
title_full	Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation
title_fullStr	Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation
title_full_unstemmed	Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation
title_sort	kinetochores require oligomerization of dam1 complex to maintain microtubule attachments against tension and promote biorientation
description	Kinetochores assemble on centromeric DNA and present arrays of proteins that attach directly to the dynamic ends of microtubules. Kinetochore proteins coordinate at the microtubule interface through oligomerization, but how oligomerization contributes to kinetochore function has remained unclear. Here, using a combination of biophysical assays and live-cell imaging, we find that oligomerization of the Dam1 kinetochore complex is required for its ability to form microtubule attachments that are robust against tension in vitro and in vivo. An oligomerization-deficient Dam1 complex that retains wild-type microtubule binding activity is primarily defective in coupling to disassembling microtubule ends under mechanical loads applied by a laser trap in vitro. In cells, the oligomerization-deficient Dam1 complex is unable to support stable bipolar alignment of sister chromatids, indicating failure of kinetochore-microtubule attachments under tension. We propose that oligomerization is an essential and conserved feature of kinetochore components that is required for accurate chromosome segregation during mitosis.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197110/
_version_	1613144780691210240

Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation

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