TY - JOUR T1 - Cdc14 phosphatase ensures resolution of aberrant meiotic recombination outcomes partly through activating Yen1/GEN1 JF - bioRxiv DO - 10.1101/571083 SP - 571083 AU - Carolina Pascual-Silva AU - Katerina Strouhalova AU - George B. Garside AU - Meret Arter AU - David Álvarez-Melo AU - Teresa Bermejo AU - Pedro San-Segundo AU - Joao Matos AU - Marco Geymonat AU - Jesús A. Carballo Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/03/14/571083.abstract N2 - Meiotic defects derived from incorrect DNA repair during gametogenesis can lead to mutations, aneuploidies and infertility. Effective and coordinated resolution of meiotic recombination intermediates is necessary to accomplish both rounds of successful chromosome segregation. Cdc14 is an evolutionarily conserved dual-specificity phosphatase required for mitotic exit and meiotic progression. Mutations that inactivate the phosphatase lead to meiotic failure. Here, we have identified previously unseen roles of Cdc14 in ensuring correct meiotic recombination. We found that aberrant recombination intermediates accumulate during prophase I when Cdc14 protein levels are drastically reduced. Furthermore, Cdc14 plays a role in suppressing the formation of non-allelic (ectopic) recombination products. We also demonstrate that Cdc14 is required for correct sister chromatid disjunction during the second meiotic divisions. Finally, Cdc14 is required in meiosis for the timely activation of the conserved Holliday Junction resolvase, Yen1/GEN1 in anaphase II. Based on these new findings we propose an early function for Cdc14 in meiotic recombination independent of its later roles during anaphase I/II.Author Summary Meiotic recombination is fundamental for sexual reproduction, effective and coordinated resolution of recombination intermediates is critical for correct chromosome segregation. Homologous recombination is initiated by the introduction of programmed DSBs followed by the formation of complex branched DNA intermediates, including double Holliday Junctions (dHJs). These recombination intermediates are eventually repaired into crossover or non-crossover products. In some cases, unresolved recombination intermediates, or toxic repair products, might persist until the metaphase to anaphase transition, requiring of a subset of late-acting repairing enzymes to process them. Unrestrained activity of these enzymes might equally put at risk the genome integrity, thus, several layers of regulation tightly control them. For example, in budding yeast meiosis, Yen1/GEN1 is only activated during the second meiotic division, although how it is activated is unknown. Here, we have identified the requirement of the Cdc14 phosphatase for the timely activation of Yen1 during the second division in meiotic cells. Additionally, we have been able to identify a previously undescribed role of Cdc14 in meiotic recombination. Strikingly, we found that levels of aberrant recombination intermediates accumulate during prophase I in cdc14 meiotic deficient cells. Furthermore, in the absence of Cdc14 activity, there is an increase of ectopic recombination products, indicating that Cdc14 plays a direct role in monitoring meiotic DSB repair, possibly in a way independent of Yen1. Such accumulation of persistent recombination intermediates is not sensed by the checkpoint machinery at the end of prophase I, and their abnormal accumulation in cdc14 meiotic cells likely contribute to the missegregation problems observed during the second meiotic division. ER -