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.

Center for Biological Research Margarita Salas Department of Cellular and Molecular Biology Spanish National Research Council Ramiro de Maeztu 9 28040 Madrid Spain

Department of Cell Biology Charles University Viničná 7 12843 Prague Czech Republic

Department of Genetics University of Cambridge Downing Street Cambridge CB2 3EH UK

Genome Damage and Stability Centre University of Sussex Brighton BN1 4DY UK

Institute of Biochemistry HPM D6 5 ETH Zürich Otto Stern Weg 3 8093 Zürich Switzerland

Institute of Functional Biology and Genomics and University of Salamanca 37007 Salamanca Spain

Leibniz Institute for Age Research Fritz Lipmann Institute Beutenbergstr 11 D 07745 Jena Germany

Max Perutz Labs University of Vienna Dr Bohr Gasse 9 1030 Vienna Austria

Memorial Sloan Kettering Cancer Center New York NY 10065 USA

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