The Monopolin Complex Crosslinks Kinetochore Components to Regulate Chromosome-Microtubule Attachments

The monopolin complex regulates different types of kinetochore-microtubule attachments in fungi, ensuring sister chromatid co-orientation in Saccharomyces cerevisiae meiosis I and inhibiting merotelic attachment in Schizosaccharomyces pombe mitosis. In addition, the monopolin complex maintains the i...

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Main Authors: Corbett, Kevin D., Yip, Calvin K., Ee, Ly-Sha, Walz, Thomas, Harrison, Stephen C., Amon, Angelika B
Other Authors: Koch Institute for Integrative Cancer Research at MIT
Format: Article
Language:en_US
Published: Elsevier B.V. 2013
Online Access:http://hdl.handle.net/1721.1/82908
https://orcid.org/0000-0001-9837-0314
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author Corbett, Kevin D.
Yip, Calvin K.
Ee, Ly-Sha
Walz, Thomas
Harrison, Stephen C.
Amon, Angelika B
author2 Koch Institute for Integrative Cancer Research at MIT
author_facet Koch Institute for Integrative Cancer Research at MIT
Corbett, Kevin D.
Yip, Calvin K.
Ee, Ly-Sha
Walz, Thomas
Harrison, Stephen C.
Amon, Angelika B
author_sort Corbett, Kevin D.
collection MIT
description The monopolin complex regulates different types of kinetochore-microtubule attachments in fungi, ensuring sister chromatid co-orientation in Saccharomyces cerevisiae meiosis I and inhibiting merotelic attachment in Schizosaccharomyces pombe mitosis. In addition, the monopolin complex maintains the integrity and silencing of ribosomal DNA (rDNA) repeats in the nucleolus. We show here that the S. cerevisiae Csm1/Lrs4 monopolin subcomplex has a distinctive V-shaped structure, with two pairs of protein-protein interaction domains positioned ∼10 nm apart. Csm1 presents a conserved hydrophobic surface patch that binds two kinetochore proteins: Dsn1, a subunit of the outer-kinetochore MIND/Mis12 complex, and Mif2/CENP-C. Csm1 point-mutations that disrupt kinetochore-subunit binding also disrupt sister chromatid co-orientation in S. cerevisiae meiosis I. We further show that the same Csm1 point-mutations affect rDNA silencing, probably by disrupting binding to the rDNA-associated protein Tof2. We propose that Csm1/Lrs4 functions as a molecular clamp, crosslinking kinetochore components to enforce sister chromatid co-orientation in S. cerevisiae meiosis I and to suppress merotelic attachment in S. pombe mitosis, and crosslinking rDNA repeats to aid rDNA silencing.
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spelling mit-1721.1/829082022-10-01T05:41:03Z The Monopolin Complex Crosslinks Kinetochore Components to Regulate Chromosome-Microtubule Attachments Corbett, Kevin D. Yip, Calvin K. Ee, Ly-Sha Walz, Thomas Harrison, Stephen C. Amon, Angelika B Koch Institute for Integrative Cancer Research at MIT Ee, Ly-Sha Amon, Angelika B. The monopolin complex regulates different types of kinetochore-microtubule attachments in fungi, ensuring sister chromatid co-orientation in Saccharomyces cerevisiae meiosis I and inhibiting merotelic attachment in Schizosaccharomyces pombe mitosis. In addition, the monopolin complex maintains the integrity and silencing of ribosomal DNA (rDNA) repeats in the nucleolus. We show here that the S. cerevisiae Csm1/Lrs4 monopolin subcomplex has a distinctive V-shaped structure, with two pairs of protein-protein interaction domains positioned ∼10 nm apart. Csm1 presents a conserved hydrophobic surface patch that binds two kinetochore proteins: Dsn1, a subunit of the outer-kinetochore MIND/Mis12 complex, and Mif2/CENP-C. Csm1 point-mutations that disrupt kinetochore-subunit binding also disrupt sister chromatid co-orientation in S. cerevisiae meiosis I. We further show that the same Csm1 point-mutations affect rDNA silencing, probably by disrupting binding to the rDNA-associated protein Tof2. We propose that Csm1/Lrs4 functions as a molecular clamp, crosslinking kinetochore components to enforce sister chromatid co-orientation in S. cerevisiae meiosis I and to suppress merotelic attachment in S. pombe mitosis, and crosslinking rDNA repeats to aid rDNA silencing. Helen Hay Whitney Foundation Howard Hughes Medical Institute Jane Coffin Childs Memorial Fund for Medical Research (Postdoctoral fellowship) 2013-12-10T21:24:17Z 2013-12-10T21:24:17Z 2010-08 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/82908 Corbett, Kevin D., Calvin K. Yip, Ly-Sha Ee, Thomas Walz, Angelika Amon, and Stephen C. Harrison. “The Monopolin Complex Crosslinks Kinetochore Components to Regulate Chromosome-Microtubule Attachments.” Cell 142, no. 4 (August 2010): 556-567. https://orcid.org/0000-0001-9837-0314 en_US http://dx.doi.org/10.1016/j.cell.2010.07.017 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier B.V. Elsevier Open Archive
spellingShingle Corbett, Kevin D.
Yip, Calvin K.
Ee, Ly-Sha
Walz, Thomas
Harrison, Stephen C.
Amon, Angelika B
The Monopolin Complex Crosslinks Kinetochore Components to Regulate Chromosome-Microtubule Attachments
title The Monopolin Complex Crosslinks Kinetochore Components to Regulate Chromosome-Microtubule Attachments
title_full The Monopolin Complex Crosslinks Kinetochore Components to Regulate Chromosome-Microtubule Attachments
title_fullStr The Monopolin Complex Crosslinks Kinetochore Components to Regulate Chromosome-Microtubule Attachments
title_full_unstemmed The Monopolin Complex Crosslinks Kinetochore Components to Regulate Chromosome-Microtubule Attachments
title_short The Monopolin Complex Crosslinks Kinetochore Components to Regulate Chromosome-Microtubule Attachments
title_sort monopolin complex crosslinks kinetochore components to regulate chromosome microtubule attachments
url http://hdl.handle.net/1721.1/82908
https://orcid.org/0000-0001-9837-0314
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