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A dCas9-Based System Identifies a Central Role for Ctf19 in Kinetochore-Derived Suppression of Meiotic Recombination

In meiosis, crossover (CO) formation between homologous chromosomes is essential for faithful segregation. However, misplaced meiotic recombination can have catastrophic consequences on genome stability. Within pericentromeres, COs are associated with meiotic chromosome missegregation. In organisms...

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Autores principales: Kuhl, Lisa-Marie, Makrantoni, Vasso, Recknagel, Sarah, Vaze, Animish N., Marston, Adele L., Vader, Gerben
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536843/
https://www.ncbi.nlm.nih.gov/pubmed/32843356
http://dx.doi.org/10.1534/genetics.120.303384
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author Kuhl, Lisa-Marie
Makrantoni, Vasso
Recknagel, Sarah
Vaze, Animish N.
Marston, Adele L.
Vader, Gerben
author_facet Kuhl, Lisa-Marie
Makrantoni, Vasso
Recknagel, Sarah
Vaze, Animish N.
Marston, Adele L.
Vader, Gerben
author_sort Kuhl, Lisa-Marie
collection PubMed
description In meiosis, crossover (CO) formation between homologous chromosomes is essential for faithful segregation. However, misplaced meiotic recombination can have catastrophic consequences on genome stability. Within pericentromeres, COs are associated with meiotic chromosome missegregation. In organisms ranging from yeast to humans, pericentromeric COs are repressed. We previously identified a role for the kinetochore-associated Ctf19 complex (Ctf19c) in pericentromeric CO suppression. Here, we develop a dCas9/CRISPR-based system that allows ectopic targeting of Ctf19c-subunits. Using this approach, we query sufficiency in meiotic CO suppression, and identify Ctf19 as a mediator of kinetochore-associated CO control. The effect of Ctf19 is encoded in its NH2-terminal tail, and depends on residues important for the recruitment of the Scc2-Scc4 cohesin regulator. This work provides insight into kinetochore-derived control of meiotic recombination. We establish an experimental platform to investigate and manipulate meiotic CO control. This platform can easily be adapted in order to investigate other aspects of chromosome biology.
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spelling pubmed-75368432020-10-14 A dCas9-Based System Identifies a Central Role for Ctf19 in Kinetochore-Derived Suppression of Meiotic Recombination Kuhl, Lisa-Marie Makrantoni, Vasso Recknagel, Sarah Vaze, Animish N. Marston, Adele L. Vader, Gerben Genetics Investigations In meiosis, crossover (CO) formation between homologous chromosomes is essential for faithful segregation. However, misplaced meiotic recombination can have catastrophic consequences on genome stability. Within pericentromeres, COs are associated with meiotic chromosome missegregation. In organisms ranging from yeast to humans, pericentromeric COs are repressed. We previously identified a role for the kinetochore-associated Ctf19 complex (Ctf19c) in pericentromeric CO suppression. Here, we develop a dCas9/CRISPR-based system that allows ectopic targeting of Ctf19c-subunits. Using this approach, we query sufficiency in meiotic CO suppression, and identify Ctf19 as a mediator of kinetochore-associated CO control. The effect of Ctf19 is encoded in its NH2-terminal tail, and depends on residues important for the recruitment of the Scc2-Scc4 cohesin regulator. This work provides insight into kinetochore-derived control of meiotic recombination. We establish an experimental platform to investigate and manipulate meiotic CO control. This platform can easily be adapted in order to investigate other aspects of chromosome biology. Genetics Society of America 2020-10 2020-08-25 /pmc/articles/PMC7536843/ /pubmed/32843356 http://dx.doi.org/10.1534/genetics.120.303384 Text en Copyright © 2020 Kuhl et al. Available freely online through the author-supported open access option. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigations
Kuhl, Lisa-Marie
Makrantoni, Vasso
Recknagel, Sarah
Vaze, Animish N.
Marston, Adele L.
Vader, Gerben
A dCas9-Based System Identifies a Central Role for Ctf19 in Kinetochore-Derived Suppression of Meiotic Recombination
title A dCas9-Based System Identifies a Central Role for Ctf19 in Kinetochore-Derived Suppression of Meiotic Recombination
title_full A dCas9-Based System Identifies a Central Role for Ctf19 in Kinetochore-Derived Suppression of Meiotic Recombination
title_fullStr A dCas9-Based System Identifies a Central Role for Ctf19 in Kinetochore-Derived Suppression of Meiotic Recombination
title_full_unstemmed A dCas9-Based System Identifies a Central Role for Ctf19 in Kinetochore-Derived Suppression of Meiotic Recombination
title_short A dCas9-Based System Identifies a Central Role for Ctf19 in Kinetochore-Derived Suppression of Meiotic Recombination
title_sort dcas9-based system identifies a central role for ctf19 in kinetochore-derived suppression of meiotic recombination
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536843/
https://www.ncbi.nlm.nih.gov/pubmed/32843356
http://dx.doi.org/10.1534/genetics.120.303384
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