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Epigenetic Dysregulation of Mammalian Male Meiosis Caused by Interference of Recombination and Synapsis
Article

The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint

1
Instituto de Biología Funcional y Genómica (IBFG), Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca, 37007 Salamanca, Spain
2
Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CSIC), 28040 Madrid, Spain
3
Departamento de Microbiología y Genética, University of Salamanca, 37007 Salamanca, Spain
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Miguel Vicente Manzanares, José M. Fuentes, Elena Llano and Pablo Martín-Vasallo
Cells 2021, 10(10), 2561; https://doi.org/10.3390/cells10102561
Received: 2 September 2021 / Revised: 22 September 2021 / Accepted: 22 September 2021 / Published: 27 September 2021
(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Spain)
During meiosis, the budding yeast polo-like kinase Cdc5 is a crucial driver of the prophase I to meiosis I (G2/M) transition. The meiotic recombination checkpoint restrains cell cycle progression in response to defective recombination to ensure proper distribution of intact chromosomes to the gametes. This checkpoint detects unrepaired DSBs and initiates a signaling cascade that ultimately inhibits Ndt80, a transcription factor required for CDC5 gene expression. Previous work revealed that overexpression of CDC5 partially alleviates the checkpoint-imposed meiotic delay in the synaptonemal complex-defective zip1Δ mutant. Here, we show that overproduction of a Cdc5 version (Cdc5-ΔN70), lacking the N-terminal region required for targeted degradation of the protein by the APC/C complex, fails to relieve the zip1Δ-induced meiotic delay, despite being more stable and reaching increased protein levels. However, precise mutation of the consensus motifs for APC/C recognition (D-boxes and KEN) has no effect on Cdc5 stability or function during meiosis. Compared to the zip1Δ single mutant, the zip1Δ cdc5-ΔN70 double mutant exhibits an exacerbated meiotic block and reduced levels of Ndt80 consistent with persistent checkpoint activity. Finally, using a CDC5-inducible system, we demonstrate that the N-terminal region of Cdc5 is essential for its checkpoint erasing function. Thus, our results unveil an additional layer of regulation of polo-like kinase function in meiotic cell cycle control. View Full-Text
Keywords: meiosis; meiotic recombination checkpoint; Cdc5; polo kinase; yeast meiosis; meiotic recombination checkpoint; Cdc5; polo kinase; yeast
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MDPI and ACS Style

González-Arranz, S.; Acosta, I.; Carballo, J.A.; Santos, B.; San-Segundo, P.A. The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint. Cells 2021, 10, 2561. https://doi.org/10.3390/cells10102561

AMA Style

González-Arranz S, Acosta I, Carballo JA, Santos B, San-Segundo PA. The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint. Cells. 2021; 10(10):2561. https://doi.org/10.3390/cells10102561

Chicago/Turabian Style

González-Arranz, Sara, Isabel Acosta, Jesús A. Carballo, Beatriz Santos, and Pedro A. San-Segundo 2021. "The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint" Cells 10, no. 10: 2561. https://doi.org/10.3390/cells10102561

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