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The Cdc14 Phosphatase Controls Resolution of Recombination Intermediates and Crossover Formation during Meiosis
Paula Alonso-Ramos1, David Álvarez-Melo1, Katerina Strouhalova1,2
1Center for Biological Research Margarita Salas, Department of Cellular and Molecular Biology, Spanish National Research Council (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain.
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.
Insights
The Cdc14 phosphatase is essential for DNA repair during meiosis, ensuring proper chromosome segregation and preventing infertility. This study reveals its direct role in regulating meiotic recombination and resolving DNA structures.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- Meiotic errors in DNA repair during gametogenesis can cause infertility and genetic abnormalities.
- Proper resolution of meiotic recombination intermediates is critical for accurate chromosome segregation.
- While kinases are known regulators, the role of phosphatases like Cdc14 in meiotic recombination is less understood.
Purpose of the Study:
- To investigate the direct role of the Cdc14 phosphatase in meiotic recombination.
- To elucidate the functions of Cdc14 in processing and resolving recombination intermediates.
- To determine Cdc14's involvement in regulating Holliday Junction resolvase Yen1/GEN1 activity.
Main Methods:
- Investigating meiotic defects in Cdc14-deficient organisms.
- Analyzing the processing and resolution of meiotic recombination intermediates.
- Assessing the activity and localization of Yen1/GEN1 in the presence and absence of Cdc14.
Main Results:
- Elimination of Cdc14 caused severe defects in recombination intermediate processing and resolution, significantly reducing crossovers.
- Cdc14 is required for the proper activity and localization of the Holliday Junction resolvase Yen1/GEN1.
- Cdc14 regulates Yen1 activity from meiosis I, crucial for crossover resolution when other pathways are impaired.
- Cdc14 and Yen1 are essential for sister chromatid segregation during meiosis II, independent of their role in crossover formation.
Conclusions:
- Cdc14 phosphatase plays a critical, previously unrecognized role in regulating meiotic recombination.
- Cdc14 directly influences the processing and resolution of recombination intermediates by regulating Yen1/GEN1.
- Cdc14 and Yen1 are vital for accurate chromosome segregation in both meiotic divisions.
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