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The Cdc14 Phosphatase Controls Resolution of Recombination Intermediates and Crossover Formation during Meiosis

Authors :
Paula Alonso-Ramos
David Álvarez-Melo
Katerina Strouhalova
Carolina Pascual-Silva
George B. Garside
Meret Arter
Teresa Bermejo
Rokas Grigaitis
Rahel Wettstein
Marta Fernández-Díaz
Joao Matos
Marco Geymonat
Pedro A. San-Segundo
Jesús A. Carballo
Source :
International Journal of Molecular Sciences, Vol 22, Iss 18, p 9811 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Meiotic defects derived from incorrect DNA repair during gametogenesis can lead to mutations, aneuploidies and infertility. The coordinated resolution of meiotic recombination intermediates is required for crossover formation, ultimately necessary for the accurate completion of both rounds of chromosome segregation. Numerous master kinases orchestrate the correct assembly and activity of the repair machinery. Although much less is known, the reversal of phosphorylation events in meiosis must also be key to coordinate the timing and functionality of repair enzymes. Cdc14 is a crucial phosphatase required for the dephosphorylation of multiple CDK1 targets in many eukaryotes. Mutations that inactivate this phosphatase lead to meiotic failure, but until now it was unknown if Cdc14 plays a direct role in meiotic recombination. Here, we show that the elimination of Cdc14 leads to severe defects in the processing and resolution of recombination intermediates, causing a drastic depletion in crossovers when other repair pathways are compromised. We also show that Cdc14 is required for the correct activity and localization of the Holliday Junction resolvase Yen1/GEN1. We reveal that Cdc14 regulates Yen1 activity from meiosis I onwards, and this function is essential for crossover resolution in the absence of other repair pathways. We also demonstrate that Cdc14 and Yen1 are required to safeguard sister chromatid segregation during the second meiotic division, a late action that is independent of the earlier role in crossover formation. Thus, this work uncovers previously undescribed functions of the evolutionary conserved Cdc14 phosphatase in the regulation of meiotic recombination.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
22
Issue :
18
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.9d7dda680fbe4be098114582facf4330
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms22189811