Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197110/
https://www.ncbi.nlm.nih.gov/pubmed/25236177
http://dx.doi.org/10.1038/ncomms5951
_version_ 1782339565886898176
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.
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.
collection PubMed
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.
format Online
Article
Text
id pubmed-4197110
institution National Center for Biotechnology Information
language English
publishDate 2014
record_format MEDLINE/PubMed
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. Nat Commun 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
spellingShingle Article
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
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197110/
https://www.ncbi.nlm.nih.gov/pubmed/25236177
http://dx.doi.org/10.1038/ncomms5951
work_keys_str_mv AT umbreitneilt kinetochoresrequireoligomerizationofdam1complextomaintainmicrotubuleattachmentsagainsttensionandpromotebiorientation
AT millermatthewp kinetochoresrequireoligomerizationofdam1complextomaintainmicrotubuleattachmentsagainsttensionandpromotebiorientation
AT tienjerryf kinetochoresrequireoligomerizationofdam1complextomaintainmicrotubuleattachmentsagainsttensionandpromotebiorientation
AT cattinortolajerome kinetochoresrequireoligomerizationofdam1complextomaintainmicrotubuleattachmentsagainsttensionandpromotebiorientation
AT guilong kinetochoresrequireoligomerizationofdam1complextomaintainmicrotubuleattachmentsagainsttensionandpromotebiorientation
AT leekellyk kinetochoresrequireoligomerizationofdam1complextomaintainmicrotubuleattachmentsagainsttensionandpromotebiorientation
AT bigginssue kinetochoresrequireoligomerizationofdam1complextomaintainmicrotubuleattachmentsagainsttensionandpromotebiorientation
AT asburycharlesl kinetochoresrequireoligomerizationofdam1complextomaintainmicrotubuleattachmentsagainsttensionandpromotebiorientation
AT davistrishan kinetochoresrequireoligomerizationofdam1complextomaintainmicrotubuleattachmentsagainsttensionandpromotebiorientation