A dCas9-based system identifies a central role for Ctf19 in kinetochore-derived suppression of meiotic recombination

Lisa Marie Kuhl, Vasso Makrantoni, Sarah Recknagel, Animish N. Vaze, Adele L. Marston, Gerben Vader*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)395-408
Number of pages14
JournalGenetics
Volume216
Issue number2
DOIs
Publication statusPublished - 1 Oct 2020

Keywords

  • CRISPR
  • DCas9
  • Kinetochore
  • Meiosis
  • Recombination

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