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Title: The Kinetochore Receptor for the Cohesin Loading Complex

Abstract

The ring-shaped cohesin complex brings together distant DNA domains to maintain, express, and segregate the genome. Establishing specific chromosomal linkages depends on cohesin recruitment to defined loci. One such locus is the budding yeast centromere, which is a paradigm for targeted cohesin loading. The kinetochore, a multiprotein complex that connects centromeres to microtubules, drives the recruitment of high levels of cohesin to link sister chromatids together. We have exploited this system to determine the mechanism of specific cohesin recruitment. We show that phosphorylation of the Ctf19 kinetochore protein by a conserved kinase, DDK, provides a binding site for the Scc2/4 cohesin loading complex, thereby directing cohesin loading to centromeres. A similar mechanism targets cohesin to chromosomes in vertebrates. These findings represent a complete molecular description of targeted cohesin loading, a phenomenon with wide-ranging importance in chromosome segregation and, in multicellular organisms, transcription regulation.

Authors:
 [1];  [2];  [3];  [2]
  1. Harvard Medical School, Boston, MA (United States)
  2. Univ. of Edinburgh (United Kingdom)
  3. Harvard Medical School, Boston, MA (United States); Howard Hughes Medical Inst., Chevy Chase, MD (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
Wellcome Centre for Cell Biology; National Institutes of Health (NIH)
OSTI Identifier:
1430320
Grant/Contract Number:  
203149; P41 GM 103403
Resource Type:
Accepted Manuscript
Journal Name:
Cell
Additional Journal Information:
Journal Volume: 171; Journal Issue: 1; Journal ID: ISSN 0092-8674
Publisher:
Elsevier
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; centromere; cohesin; kinetochore; cell cycle

Citation Formats

Hinshaw, Stephen M., Makrantoni, Vasso, Harrison, Stephen C., and Marston, Adèle L. The Kinetochore Receptor for the Cohesin Loading Complex. United States: N. p., 2017. Web. doi:10.1016/j.cell.2017.08.017.
Hinshaw, Stephen M., Makrantoni, Vasso, Harrison, Stephen C., & Marston, Adèle L. The Kinetochore Receptor for the Cohesin Loading Complex. United States. https://doi.org/10.1016/j.cell.2017.08.017
Hinshaw, Stephen M., Makrantoni, Vasso, Harrison, Stephen C., and Marston, Adèle L. Thu . "The Kinetochore Receptor for the Cohesin Loading Complex". United States. https://doi.org/10.1016/j.cell.2017.08.017. https://www.osti.gov/servlets/purl/1430320.
@article{osti_1430320,
title = {The Kinetochore Receptor for the Cohesin Loading Complex},
author = {Hinshaw, Stephen M. and Makrantoni, Vasso and Harrison, Stephen C. and Marston, Adèle L.},
abstractNote = {The ring-shaped cohesin complex brings together distant DNA domains to maintain, express, and segregate the genome. Establishing specific chromosomal linkages depends on cohesin recruitment to defined loci. One such locus is the budding yeast centromere, which is a paradigm for targeted cohesin loading. The kinetochore, a multiprotein complex that connects centromeres to microtubules, drives the recruitment of high levels of cohesin to link sister chromatids together. We have exploited this system to determine the mechanism of specific cohesin recruitment. We show that phosphorylation of the Ctf19 kinetochore protein by a conserved kinase, DDK, provides a binding site for the Scc2/4 cohesin loading complex, thereby directing cohesin loading to centromeres. A similar mechanism targets cohesin to chromosomes in vertebrates. These findings represent a complete molecular description of targeted cohesin loading, a phenomenon with wide-ranging importance in chromosome segregation and, in multicellular organisms, transcription regulation.},
doi = {10.1016/j.cell.2017.08.017},
journal = {Cell},
number = 1,
volume = 171,
place = {United States},
year = {Thu Sep 21 00:00:00 EDT 2017},
month = {Thu Sep 21 00:00:00 EDT 2017}
}

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Cited by: 65 works
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