Casein Kinase 1 Coordinates Cohesin Cleavage, Gametogenesis, and Exit from M Phase in Meiosis II

Argüello-Miranda, Orlando; Zagoriy, Ievgeniia; Mengoli, Valentina; Rojas, Julie; Jonak, Katarzyna; Oz, Tugce; Graf, Peter; Zachariae, Wolfgang

doi:10.1016/j.devcel.2016.11.021

Cited by 51 publications

(106 citation statements)

References 42 publications

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“…A very subtle delay, observed during both divisions, could in part arise from difficulties in SPB re-duplication and half-bridge separation, as described in cdc14-1 cells [55]. Similarly, inactivation of Cdc14 in cells transiting metaphase II, did not show any effect on the lifetime of meiosis II spindles [94], confirming that the phenotype we observe can be reproduced under different modes of cdc14 inactivation during meiosis. Moreover, the meiotic delays observed in cdc14 3HA are not restricted to the completion of meiotic divisions.…”

Section: Novel Insights Into Cdc14 Functionalities By Using An Epitopsupporting

confidence: 79%

“…We exclude that the process of spore formation was affected since we visualized pro-spore membrane components appearing at similar kinetics in the mutant strain as they did in the wild type (S6 Fig). Other groups have also described similar defects in sporulation in the absence of Cdc14 activity, or components of the MEN pathway [48,94]. The fact that we monitored correct SPB re-duplication and separation in a high proportion of cdc14 3HA cells (Fig 2C-D; S3 Fig), and that they are able to assemble functional spindles at metaphase/anaphase II also confirms that problems arising in cdc14 3HA mutant somewhat differ from those already described for the widely employed, thermo-sensitive alleles, cdc14-1, -3 or other FEAR mutants [45,53,55].…”

Section: Novel Insights Into Cdc14 Functionalities By Using An Epitopmentioning

confidence: 74%

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The Cdc14 phosphatase controls resolution of recombination intermediates and crossover formation during meiosis

Alonso-Ramos

Álvarez-Melo

Strouhalova

et al. 2019

Preprint

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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. 2 Author SummaryMeiotic 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.

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Section: Novel Insights Into Cdc14 Functionalities By Using An Epitopsupporting

confidence: 79%

Section: Novel Insights Into Cdc14 Functionalities By Using An Epitopmentioning

confidence: 74%

The Cdc14 phosphatase controls resolution of recombination intermediates and crossover formation during meiosis

Alonso-Ramos

Álvarez-Melo

Strouhalova

et al. 2019

Preprint

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“…To analyze chromatid segregation at meiosis II in budding yeast, we developed a synchronisation system, called CDC20-meioticarrest/release or CDC20-mAR, which is capable of resolving meiosis I and -II. 43 With the help of a mitosis-specific promoter, cells induced to enter meiosis are depleted of the APC/C activator Cdc20, which leads to a uniform arrest at metaphase I. Expression of a second copy of CDC20 under the control of a copper-inducible promoter results in synchronous progression through both meiotic divisions and the formation of viable spores.…”

Section: A Model For Apc/c Cdc20 -Dependent Deprotection Of Centromermentioning

confidence: 99%

APC/C-Cdc20 mediates deprotection of centromeric cohesin at meiosis II in yeast

Jonak

Zagoriy

et al. 2017

Cell Cycle

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Cells undergoing meiosis produce haploid gametes through one round of DNA replication followed by 2 rounds of chromosome segregation. This requires that cohesin complexes, which establish sister chromatid cohesion during S phase, are removed in a stepwise manner. At meiosis I, the separase protease triggers the segregation of homologous chromosomes by cleaving cohesin's Rec8 subunit on chromosome arms. Cohesin persists at centromeres because the PP2A phosphatase, recruited by the shugoshin protein, dephosphorylates Rec8 and thereby protects it from cleavage. While chromatids disjoin upon cleavage of centromeric Rec8 at meiosis II, it was unclear how and when centromeric Rec8 is liberated from its protector PP2A. One proposal is that bipolar spindle forces separate PP2A from Rec8 as cells enter metaphase II. We show here that sister centromere biorientation is not sufficient to "deprotect" Rec8 at meiosis II in yeast. Instead, our data suggest that the ubiquitin-ligase APC/C removes PP2A from centromeres by targeting for degradation the shugoshin Sgo1 and the kinase Mps1. This implies that Rec8 remains protected until entry into anaphase II when it is phosphorylated concurrently with the activation of separase. Here, we provide further support for this model and speculate on its relevance to mammalian oocytes.

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“…Rec8 cleavage is dependent on its prior phosphorylation by three kinases -casein kinase 1δ (Hrr25), Dbf4-dependent kinase (DDK) Cdc7 (Katis et al 2010) and Polo kinase (Cdc5) (Brar et al 2006). However, it is currently unclear how these kinases contribute to cohesin removal with the role of Cdc5 in cohesin cleavage coming under particular scrutiny (Brar et al 2006;Katis et al 2010;Attner et al 2013;Argüello-Miranda et al 2017). While cohesin phosphorylation occurs along the length of the chromosome, the pericentromeric adapter protein shugoshin (Sgo1) binds protein phosphatase 2A (PP2A) to dephosphorylate Rec8 in the pericentromere and prevent its cleavage (Kitajima et al 2004;Katis et al 2004a;Kitajima et al 2006;Tang et al 2006;Riedel et al 2006;Lee et al 2008).…”

Section: Introductionmentioning

confidence: 99%

“…While cohesin phosphorylation occurs along the length of the chromosome, the pericentromeric adapter protein shugoshin (Sgo1) binds protein phosphatase 2A (PP2A) to dephosphorylate Rec8 in the pericentromere and prevent its cleavage (Kitajima et al 2004;Katis et al 2004a;Kitajima et al 2006;Tang et al 2006;Riedel et al 2006;Lee et al 2008). In meiosis II, Rec8 becomes deprotected by the action of Hrr25, which is thought to initiate Sgo1 degradation and phosphorylate Rec8 for cleavage (Argüello-Miranda et al 2017;Jonak et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Spo13 prevents premature cohesin cleavage during meiosis

Galander

Barton

Kelly

et al. 2018

Preprint

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Meiosis produces gametes through two successive nuclear divisions, meiosis I and meiosis II. In contrast to mitosis and meiosis II, where sister chromatids are segregated, during meiosis I, homologous chromosomes are segregated. This requires the monopolar attachment of sister kinetochores and the loss of cohesion from chromosome arms, but not centromeres, during meiosis I. The establishment of both sister kinetochore mono-orientation and cohesion protection rely on the budding yeast meiosis I-specific Spo13 protein, the functional homolog of fission yeast Moa1 and mouse MEIKIN. Here we investigate the effects of loss of SPO13 on cohesion during meiosis I. Unlike wild type, cells lacking SPO13 fail to maintain the meiosis-specific cohesin subunit, Rec8, at centromeres and segregate sister chromatids to opposite poles during anaphase I. We show that the cohesin-destabilizing factor, Wpl1, is not primarily responsible for the loss of cohesion during meiosis I. Instead, premature loss of centromeric cohesin during anaphase I in spo13Δ cells relies on separasedependent cohesin cleavage. Further, cohesin loss in spo13Δ anaphase I cells is blocked by forcibly tethering the regulatory subunit of protein phosphatase 2A, Rts1, to Rec8. Our findings indicate that separase-dependent cleavage of phosphorylated Rec8 causes premature cohesin loss in spo13Δ cells.

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Casein Kinase 1 Coordinates Cohesin Cleavage, Gametogenesis, and Exit from M Phase in Meiosis II

Cited by 51 publications

References 42 publications

The Cdc14 phosphatase controls resolution of recombination intermediates and crossover formation during meiosis

The Cdc14 phosphatase controls resolution of recombination intermediates and crossover formation during meiosis

APC/C-Cdc20 mediates deprotection of centromeric cohesin at meiosis II in yeast

Spo13 prevents premature cohesin cleavage during meiosis

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