@article{6ff221f9761a4dcbb0e5353bac192ca9,
title = "A dCas9-based system identifies a central role for Ctf19 in kinetochore-derived suppression of meiotic recombination",
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.",
keywords = "CRISPR, DCas9, Kinetochore, Meiosis, Recombination",
author = "Kuhl, {Lisa Marie} and Vasso Makrantoni and Sarah Recknagel and Vaze, {Animish N.} and Marston, {Adele L.} and Gerben Vader",
note = "Funding Information: We thank the Vader and Bird (Max Planck Institute of Molecular Physiology, Dortmund, Germany) laboratories for ideas and helpful discussions. We thank Richard Cardoso da Silva (Max Planck Institute of Molecular Physiology, Dortmund, Germany) for mapping Spo11-oligo datasets. We acknowledge Andrea Musacchio (Max Planck Institute of Molecular Physiology, Dortmund, Germany) for ongoing support. We thank Stephen Hinshaw (Harvard Medical School, Boston, USA) for comments on the manuscript and for sharing illustrations depicting the structural organization of the budding yeast kinetochore. We acknowledge Hodaka Fujii (Hirosaki University, Hirosaki, Japan) and John Wyrick (Washington State University, Pullmann, USA) for sharing reagents. We thank John Weir (Friedrich Miescher Laboratory, T{\"u}bingen, Germany) and Vivek B. Raina (Max Planck Institute of Molecular Physiology, Dortmund, Germany) for comments on the manuscript. Work in the Vader laboratory was financially supported by the European Research Council (ERC Starting Grant URDNA, agreement nr. 638197, to G.V.) and the Max Planck Society. Work in the Marston laboratory was funded by a Wellcome Senior Research Fellowship (107827) and core funding for the Wellcome Centre for Cell Biology (203149). A.N.V. acknowledges support from INSPIRE, Department of Science and Technology (DST), Government of India, and from the Department of Biological Sciences, IISER Kolkata, India. Publisher Copyright: {\textcopyright} 2020 Genetics Society of America. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = oct,
doi = "https://doi.org/10.1534/genetics.120.303384",
language = "English",
volume = "216",
pages = "395--408",
journal = "Genetics",
issn = "0016-6731",
publisher = "Genetics Society of America",
number = "2",
}