» Articles » PMID: 34575966

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

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.

Citing Articles

Decoding the Nucleolar Role in Meiotic Recombination and Cell Cycle Control: Insights into Cdc14 Function.

Alonso-Ramos P, Carballo J Int J Mol Sci. 2024; 25(23).

PMID: 39684572 PMC: 11641746. DOI: 10.3390/ijms252312861.


CDK phosphorylation of Sfr1 downregulates Rad51 function in late-meiotic homolog invasions.

Palacios-Blanco I, Gomez L, Bort M, Mayerova N, Bagelova Polakova S, Martin-Castellanos C EMBO J. 2024; 43(19):4356-4383.

PMID: 39174851 PMC: 11445502. DOI: 10.1038/s44318-024-00205-2.


Meiotic double-strand break repair DNA synthesis tracts in Arabidopsis thaliana.

Hernandez Sanchez-Rebato M, Schubert V, White C PLoS Genet. 2024; 20(7):e1011197.

PMID: 39012914 PMC: 11280534. DOI: 10.1371/journal.pgen.1011197.


The Cdc14 phosphatase, Clp1, does not affect genome expression.

Lopez Maury L, Ren L, Hassan S, Bahler J, Gould K MicroPubl Biol. 2024; 2024.

PMID: 38415071 PMC: 10897734. DOI: 10.17912/micropub.biology.001089.


Saccharomyces cerevisiae deficient in the early anaphase release of Cdc14 can traverse anaphase I without ribosomal DNA disjunction and successfully complete meiosis.

Yellman C Biol Open. 2023; 12(10).

PMID: 37530060 PMC: 10621906. DOI: 10.1242/bio.059853.


References
1.
Queralt E, Lehane C, Novak B, Uhlmann F . Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast. Cell. 2006; 125(4):719-32. DOI: 10.1016/j.cell.2006.03.038. View

2.
Stegmeier F, Visintin R, Amon A . Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase. Cell. 2002; 108(2):207-20. DOI: 10.1016/s0092-8674(02)00618-9. View

3.
Sullivan M, Higuchi T, Katis V, Uhlmann F . Cdc14 phosphatase induces rDNA condensation and resolves cohesin-independent cohesion during budding yeast anaphase. Cell. 2004; 117(4):471-82. DOI: 10.1016/s0092-8674(04)00415-5. View

4.
Hunter N, Kleckner N . The single-end invasion: an asymmetric intermediate at the double-strand break to double-holliday junction transition of meiotic recombination. Cell. 2001; 106(1):59-70. DOI: 10.1016/s0092-8674(01)00430-5. View

5.
Visintin R, Stegmeier F, Amon A . The role of the polo kinase Cdc5 in controlling Cdc14 localization. Mol Biol Cell. 2003; 14(11):4486-98. PMC: 266767. DOI: 10.1091/mbc.e03-02-0095. View