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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Genetics Society of America
2020
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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. |
format | Online Article Text |
id | pubmed-7536843 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Genetics Society of America |
record_format | MEDLINE/PubMed |
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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