Polo-like kinase-dependent phosphorylation of the synaptonemal complex protein SYP-4 regulates double-strand break formation through a negative feedback loop.

Nadarajan, Saravanapriah; Lambert, Talley J.; Altendorfer, Elisabeth; Gao, Jinmin; Blower, Michael D.; Waters, Jennifer; Colaiácovo, Mónica P.

doi:10.7554/elife.23437

Cited by 83 publications

(130 citation statements)

References 80 publications

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“…We hypothesize that PLK-2 localization and activity then spread along the lengths of these SCs via a self-reinforcing feedback loop that in turn results in stabilization of the SC central region along the full length of the SC. This model is reinforced by the recent finding of S. Nadarajan and M. Colaiacovo [33] that SC central region protein SYP-4 is phosphorylated in a PLK-1/2-dependent manner.…”

Section: Discussionmentioning

confidence: 76%

Meiotic recombination modulates the structure and dynamics of the synaptonemal complex during C. elegans meiosis

et al. 2017

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During meiotic prophase, a structure called the synaptonemal complex (SC) assembles at the interface between aligned pairs of homologous chromosomes, and crossover recombination events occur between their DNA molecules. Here we investigate the inter-relationships between these two hallmark features of the meiotic program in the nematode C. elegans, revealing dynamic properties of the SC that are modulated by recombination. We demonstrate that the SC incorporates new subunits and switches from a more highly dynamic/labile state to a more stable state as germ cells progress through the pachytene stage of meiotic prophase. We further show that the more dynamic state of the SC is prolonged in mutants where meiotic recombination is impaired. Moreover, in meiotic mutants where recombination intermediates are present in limiting numbers, SC central region subunits become preferentially stabilized on the subset of chromosome pairs that harbor a site where pro-crossover factors COSA-1 and MutSγ are concentrated. Polo-like kinase PLK-2 becomes preferentially localized to the SCs of chromosome pairs harboring recombination sites prior to the enrichment of SC central region proteins on such chromosomes, and PLK-2 is required for this enrichment to occur. Further, late pachytene nuclei in a plk-2 mutant exhibit the more highly dynamic SC state. Together our data demonstrate that crossover recombination events elicit chromosome-autonomous stabilizing effects on the SC and implicate PLK-2 in this process. We discuss how this recombination-triggered modulation of SC state might contribute to regulatory mechanisms that operate during meiosis to ensure the formation of crossovers while at the same time limiting their numbers.

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Section: Discussionmentioning

confidence: 76%

Meiotic recombination modulates the structure and dynamics of the synaptonemal complex during C. elegans meiosis

et al. 2017

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“…Such an act would further facilitate the transition into metaphase I. Negative regulation of DSB formation by a Polo kinase has recently been reported in the worm (Nadarajan et al , ). We do not currently know whether other members of the Ndt80 regulon facilitate this role of Cdc5, although given the nature of the findings presented here, we speculate that Cdc5 does not act alone.…”

Section: Discussionmentioning

confidence: 95%

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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“…1 B and C). Two recent studies have shown that the SC progressively becomes more stable throughout the pachytene stage of prophase I, likely through the posttranslational modification of SC proteins (27,28). This gradual switch to a more stable SC could potentially alter the structure as it progresses through meiosis.…”

Section: Resultsmentioning

confidence: 99%

Superresolution expansion microscopy reveals the three-dimensional organization of theDrosophilasynaptonemal complex

Cahoon

Wang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

127

117

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The synaptonemal complex (SC), a structure highly conserved from yeast to mammals, assembles between homologous chromosomes and is essential for accurate chromosome segregation at the first meiotic division. In Drosophila melanogaster, many SC components and their general positions within the complex have been dissected through a combination of genetic analyses, superresolution microscopy, and electron microscopy. Although these studies provide a 2D understanding of SC structure in Drosophila, the inability to optically resolve the minute distances between proteins in the complex has precluded its 3D characterization. A recently described technology termed expansion microscopy (ExM) uniformly increases the size of a biological sample, thereby circumventing the limits of optical resolution. By adapting the ExM protocol to render it compatible with structured illumination microscopy, we can examine the 3D organization of several known Drosophila SC components. These data provide evidence that two layers of SC are assembled. We further speculate that each SC layer may connect two nonsister chromatids, and present a 3D model of the Drosophila SC based on these findings.synaptonemal complex | expansion microscopy | meiosis | sister chromatids | structured illumination microscopy

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Polo-like kinase-dependent phosphorylation of the synaptonemal complex protein SYP-4 regulates double-strand break formation through a negative feedback loop.

Cited by 83 publications

References 80 publications

Meiotic recombination modulates the structure and dynamics of the synaptonemal complex during C. elegans meiosis

Meiotic recombination modulates the structure and dynamics of the synaptonemal complex during C. elegans meiosis

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

Superresolution expansion microscopy reveals the three-dimensional organization of theDrosophilasynaptonemal complex

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