TY - JOUR
T1 - The cdc14 phosphatase controls resolution of recombination intermediates and crossover formation during meiosis
AU - Alonso-Ramos, Paula
AU - Álvarez-Melo, David
AU - Strouhalova, Katerina
AU - Pascual-Silva, Carolina
AU - Garside, George B.
AU - Arter, Meret
AU - Bermejo, Teresa
AU - Grigaitis, Rokas
AU - Wettstein, Rahel
AU - Fernández-Díaz, Marta
AU - Matos, Joao
AU - Geymonat, Marco
AU - San-Segundo, Pedro A.
AU - Carballo, Jesús A.
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - Aneuploidy
KW - Cdc14
KW - Cdc20
KW - Cdc5
KW - CDK1
KW - Holliday junction
KW - Meiotic recombination
KW - Mus81
KW - Ndt80
KW - Sgs1
KW - Yen1
KW - DOUBLE-STRAND BREAKS
KW - CELL-DIVISION-CYCLE
KW - COHESIN CLEAVAGE
KW - SACCHAROMYCES-CEREVISIAE
KW - meiotic recombination
KW - HOLLIDAY JUNCTION RESOLVASE
KW - SISTER CHROMATIDS
KW - POLO KINASE CDC5
KW - aneuploidy
KW - MITOTIC EXIT
KW - SYNAPTONEMAL COMPLEX-FORMATION
KW - MEIOTIC RECOMBINATION
UR - http://www.scopus.com/inward/record.url?scp=85114647365&partnerID=8YFLogxK
U2 - 10.3390/ijms22189811
DO - 10.3390/ijms22189811
M3 - Article
C2 - 34575966
AN - SCOPUS:85114647365
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 18
M1 - 9811
ER -