The synaptonemal complex is assembled by a polySUMOylation-driven feedback mechanism in yeast

Leung, Wing-Kit; Humphryes, Neil; Afshar, Negar; Argunhan, Bilge; Terentyev, Yaroslav; Tsubouchi, Tomomi; Tsubouchi, Hideo

doi:10.1083/jcb.201506103

Cited by 42 publications

(43 citation statements)

References 40 publications

(60 reference statements)

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“…These state changes may best be explained by post-translational modifications of SC subunits (or the chromosome axes which they join), including, but not limited to, phosphorylation [39] and SUMOylation [40]. Alternatively, the binding and release of additional proteins to the SC could also function in this manner.…”

Section: Discussionmentioning

confidence: 99%

A Surveillance System Ensures Crossover Formation in C. elegans

et al. 2016

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SUMMARY Crossover (CO) recombination creates a physical connection between homologs that promotes their proper segregation at meiosis I (MI). Failure to realize an obligate CO causes homologs to attach independently to the MI spindle and separate randomly, leading to nondisjunction. However, mechanisms that determine whether homolog pairs have received crossovers remain mysterious. We describe a surveillance system in C. elegans that monitors recombination intermediates and couples their formation to meiotic progression. Recombination intermediates are required to activate the system that then delays further processing if crossover precursors are lacking on even one chromosome. The synaptonemal complex, a specialized, proteinaceous structure connecting homologous chromosomes, is stabilized in cis on chromosomes that receive a crossover and destabilized on those lacking crossovers, a process that is dependent on the function of the polo-like kinase, PLK-2. These results reveal a new layer of communication between crossover-committed intermediates and the synaptonemal complex that functions as a cis-acting, obligate, crossover-counting mechanism.

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Section: Discussionmentioning

confidence: 99%

A Surveillance System Ensures Crossover Formation in C. elegans

et al. 2016

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“…It is interesting to note that other members of the Ndt80 regulon are dispensable for SC destruction, strongly suggesting that the means to destroy the SC exists before pachytene exit but is unable to act in the absence of Cdc5 activity. Emphasis should be placed on identifying the targets of Cdc5, which likely include Red1 and/or Zip1, and possibly other central element proteins that are required for SC formation such as Ecm11 and Gmc2 (Humphryes et al , ; Voelkel‐Meiman et al , ; Leung et al , ).…”

Section: Discussionmentioning

confidence: 99%

Fundamental cell cycle kinases collaborate to ensure timely destruction of the synaptonemal complex during meiosis

et al. 2017

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The synaptonemal complex (SC) is a proteinaceous macromolecular assembly that forms during meiotic prophase I and mediates adhesion of paired homologous chromosomes along their entire lengths. Although prompt disassembly of the SC during exit from prophase I is a landmark event of meiosis, the underlying mechanism regulating SC destruction has remained elusive. Here, we show that DDK (Dbf4-dependent Cdc7 kinase) is central to SC destruction. Upon exit from prophase I, Dbf4, the regulatory subunit of DDK, directly associates with and is phosphorylated by the Polo-like kinase Cdc5. In parallel, upregulated CDK1 activity also targets Dbf4. An enhanced Dbf4-Cdc5 interaction pronounced phosphorylation of Dbf4 and accelerated SC destruction, while reduced/abolished Dbf4 phosphorylation hampered destruction of SC proteins. SC destruction relieved meiotic inhibition of the ubiquitous recombinase Rad51, suggesting that the mitotic recombination machinery is reactivated following prophase I exit to repair any persisting meiotic DNA double-strand breaks. Taken together, we propose that the concerted action of DDK, Polo-like kinase, and CDK1 promotes efficient SC destruction at the end of prophase I to ensure faithful inheritance of the genome.

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“…al (2015) demonstrated that Zip1's N terminal 346 residues is sufficient to promote Ecm11 SUMOylation in vegetative (non-meiotic) cells, provided that Gmc2 is also expressed. These data suggest that the N terminal region of Zip1 is able to engage with the Ecm11-Gmc2 proteins, perhaps in a direct manner or perhaps indirectly through a protein expressed in both meiotic as well as mitotic cells [51]. Similar to the uncertainty about whether Zip3 interacts with Zip1 in a direct manner, apart from the genetic interactions found for Zip1 and Ecm11 and the coincidence of Ecm11 and Gmc2 at the midline of SC (where Zip1 N termini also reside [19]), strong evidence of a direct physical interaction between Zip1 and Ecm11 or Gmc2 does not yet exist.…”

Section: Two Functionally Distinct Regions Within Zip1's N Terminal Tmentioning

confidence: 88%

“…We previously demonstrated that zip1[D21-163] phenocopies the ecm11 and gmc2 null mutant phenotype (a failure in SC assembly but proficiency in MutSg crossing over), suggesting that this N terminal region of Zip1 functionally interacts with the central element in order to assemble SC [22]. Moreover, Leung et. al (2015) demonstrated that Zip1's N terminal 346 residues is sufficient to promote Ecm11 SUMOylation in vegetative (non-meiotic) cells, provided that Gmc2 is also expressed.…”

Section: Two Functionally Distinct Regions Within Zip1's N Terminal Tmentioning

confidence: 99%

Crossover recombination and synapsis are linked by adjacent regions within the N terminus of the Zip1 synaptonemal complex protein

Voelkel‐Meiman

Cheng

Parziale

et al. 2018

Preprint

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Accurate chromosome segregation during meiosis relies on the prior establishment of at least one crossover recombination event between homologous chromosomes, which is often associated with the meiosis-specific MutSg complex. The recombination intermediates that give rise to MutSg interhomolog crossovers are embedded within a hallmark meiotic prophase structure called the synaptonemal complex (SC), but the mechanisms that coordinate the processes of SC assembly (synapsis) and crossover recombination remain poorly understood. Among known central region building blocks of the budding yeast SC, the Zip1 protein is unique for its SCindependent role in promoting MutSg crossovers. Here we report that adjacent regions within Zip1's unstructured N terminus encompass its crossover and SC assembly functions. We previously showed that deletion of Zip1 residues 21-163 abolishes tripartite SC assembly and prevents the robust SUMOylation of the SC central element component, Ecm11, but allows excess MutSg crossover recombination. We find the reciprocal phenotype when Zip1 residues 2-9 or 10-14 are deleted; in these mutants SC assembles and Ecm11 is hyperSUMOylated, but MutSg crossovers are strongly diminished. Interestingly, Zip1 residues 2-9 or 2-14 are required for the normal localization of Zip3, a putative E3 SUMO ligase and pro-MutSg crossover factor, to Zip1 polycomplex structures and to recombination initiation sites. By contrast, deletion of Zip1 residues 15-20 does not detectably prevent Zip3's localization at Zip1 polycomplex and supports some MutSg crossing over but prevents normal SC assembly and robust Ecm11SUMOylation. These results highlight distinct N terminal regions that are differentially critical for Zip1's roles in crossover recombination and SC assembly; we speculate that the adjacency of these regions enables Zip1 to serve as a liaison, facilitating crosstalk between the two processes by bringing crossover recombination and synapsis factors in close proximity to one another.

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The synaptonemal complex is assembled by a polySUMOylation-driven feedback mechanism in yeast

Abstract: Synaptonemal complex (SC) assembly requires polySUMOylation of Ecm11, which promotes polymerization of Zip1, the transverse filament, whereas the N terminus of Zip1 activates Ecm11 polySUMOylation, suggesting that this positive feedback loop underpins SC assembly.

Cited by 42 publications

References 40 publications

A Surveillance System Ensures Crossover Formation in C. elegans

A Surveillance System Ensures Crossover Formation in C. elegans

Fundamental cell cycle kinases collaborate to ensure timely destruction of the synaptonemal complex during meiosis

Crossover recombination and synapsis are linked by adjacent regions within the N terminus of the Zip1 synaptonemal complex protein

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