Identification of novel synaptonemal complex components in <i>C. elegans</i>

Hurlock, Matthew E; Čavka, Ivana; Kursel, Lisa E; Haversat, Jocelyn; Wooten, Matthew; Nizami, Zehra F.; Turniansky, Rashi; Hoess, Philipp; Ries, Jonas; Gall, Joseph G.; Rog, Ofer; Köhler, Simone; Kim, Yumi

doi:10.1083/jcb.201910043

Cited by 47 publications

(83 citation statements)

References 75 publications

(113 reference statements)

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“…This suggests that recruitment or activation of one or more kinases that phosphorylate HIM-3 is dependent on SYP proteins. The enrichment of SC central proteins on short arms in late pachytene [4,[38][39][40][41] , coincident in location and timing with phosphorylated HIM-3 partitioning, further suggests the central element provides a platform for a kinase to phosphorylate HIM-3 preferentially on short arms upon crossover designation.…”

Section: Phosphorylated Him-3 Localizes To the Entire Length Of The Smentioning

confidence: 97%

Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase inC. elegans

Sato-Carlton

Tabuchi

et al. 2020

Preprint

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AbstractIn the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through the discrete, two-step removal of chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at the centromere until the second division. In eukaryotes without defined centromeres, however, alternative strategies have been innovated. The best-understood of these is that used by the nematode Caenorhabditis elegans, where upon division of the chromosome into two segments or arms by the single off-center crossover, several chromosome-associated proteins or post-translational modifications become specifically partitioned to either the short or long arm, where they affect the timing of cohesion loss through as-yet unknown mechanisms. Here, we investigate the meiotic axis HORMA-domain protein HIM-3 and show that it becomes phosphorylated at its C-terminus, within the conserved “closure motif” region bound by the related HORMA-domain proteins HTP-1 and HTP-2. Binding of HTP-2 is abrogated by phosphorylation of the closure motif in in vitro assays, strongly suggesting that in vivo phosphorylation of HIM-3 likely modulates the hierarchical structure of the chromosome axis. Phosphorylation of HIM-3 only occurs on synapsed chromosomes, and similarly to previously-described phosphorylated proteins of the synaptonemal complex, becomes restricted to the short arm after designation of crossover recombination sites. Regulation of HIM-3 phosphorylation status is required for timely disassembly of synaptonemal complex central elements from the long arm, and is also required for proper timing of HTP-1 and HTP-2 dissociation from the short arm. Phosphorylation of HIM-3 thus plays a role in establishing the identity of short and long arms, thereby contributing to the robustness of the two-step chromosome segregation.

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Section: Phosphorylated Him-3 Localizes To the Entire Length Of The Smentioning

confidence: 97%

Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase inC. elegans

Sato-Carlton

Tabuchi

et al. 2020

Preprint

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“…(1:500, [62]), mouse anti-GFP (1:1000, Roche 11814460001), goat anti-SYP-1 (1:500, [63]), Cy3 AffiniPure Donkey Anti-Guinea pig (1:500, Jackson Immunoresearch), Cy5 AffiniPure Donkey anti-Goat (1:500, Jackson Immunoresearch), and 488 AffiniPure Donkey anti-Mouse (1:500, Jackson Immunoresearch).…”

Section: Cytologymentioning

confidence: 99%

Meiotic sister chromatid exchanges are rare inC. elegans

Almanzar

Gordon

Rog

2020

Preprint

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Sexual reproduction shuffles the parental genomes to generate new genetic combinations. To achieve that, the genome is subjected to numerous double-strand breaks, the repair of which involves two crucial decisions: repair pathway and repair template. Use of crossover pathways with the homologous chromosome as template exchanges genetic information and directs chromosome segregation. Crossover repair, however, can compromise the integrity of the repair template and is therefore tightly regulated. The extent to which crossover pathways are used during sister-directed repair is unclear, because the identical sister chromatids are difficult to distinguish. Nonetheless, indirect assays have led to the suggestion that inter-sister crossovers, or sister chromatid exchanges (SCEs), are quite common. Here we devised a technique to directly score physiological SCEs in the C. elegans germline using selective sister chromatid labeling with the thymidine analog 5-ethynyl-2’-deoxyuridine (EdU). Surprisingly, we find SCEs to be rare in meiosis, accounting for <2% of repair events. SCEs remain rare even when the homologous chromosome is unavailable, indicating that almost all sister-directed repair is channeled into noncrossover pathways. We identify two mechanisms that limit SCEs. First, sister-directed repair intermediates are efficiently inhibited by the RecQ helicase BLMHIM-6. Second, the Synaptonemal Complex–a conserved interface that promotes crossover repair– localizes between the homologous chromosomes and not the sister chromatids. Our data suggest that in C. elegans crossover pathways are only used to generate the single necessary link between the homologous chromosomes. Almost all other breaks, regardless of which repair template they use, are repaired by noncrossover pathways.

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“…Previous analyses in oogenesis had indicated that when crossover formation is completely blocked by mutation of central components of the SC, COSA-1 accumulates at foci that represent aberrant recombination sites (LI et al 2018;WOGLAR AND VILLENEUVE 2018;HURLOCK et al 2020). We next examined GFP::COSA-1 in syp-1 mutant males, in which germ cells fail to undergo chromosome synapsis and therefore do not form any interhomolog crossovers (MACQUEEN et al 2002).…”

Section: Brc-1-brd-1 Inhibitsmentioning

confidence: 99%

C. elegans BRC-1-BRD-1 functions at an early step of DSB processing and inhibits supernumerary crossovers during male meiosis

Engebrecht

Li²,

Hariri³

2020

Preprint

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Meiosis is regulated in a sex-specific manner to produce two distinct gametes, sperm and oocytes, for sexual reproduction. To determine how meiotic recombination is regulated in spermatogenesis, we analyzed the meiotic phenotypes of mutants in the tumor suppressor E3 ubiquitin ligase BRC-1-BRD-1 complex in Caenorhabditis elegans male meiosis. Unlike in mammals, this complex is not required for meiotic sex chromosome inactivation, the process whereby hemizygous sex chromosomes are transcriptionally silenced. Interestingly, brc-1 and brd-1 mutants showed meiotic recombination phenotypes that are largely opposing to those previously reported for female meiosis.Fewer meiotic recombination foci marked by the recombinase RAD-51 were observed in brc-1 and brd-1 mutants, and the reduction in RAD-51 foci can be suppressed by mutation of nonhomologous end joining proteins. We show that concentration of BRC-1-BRD-1 to sites of meiotic recombination is dependent on DNA end resection, suggesting that BRC-1-BRD-1 regulates the processing of meiotic double strand breaks to promote repair by homologous recombination, similar to a role for the complex in somatic cells. We also show that BRC-1-BRD-1 is important to promote progeny viability when male meiosis is perturbed by mutations that block the pairing and synapsis of different chromosome pairs, although the complex is not required to stabilize the RAD-51 filament as in female meiosis under the same conditions. Analyses of crossover designation and formation reveal that BRC-1-BRD-1 inhibits supernumerary crossovers when meiosis is perturbed. Together, our findings suggest that BRC-1-BRD-1 regulates different aspects of meiotic recombination in male and female meiosis.

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Identification of novel synaptonemal complex components in C. elegans

Cited by 47 publications

References 75 publications

Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase inC. elegans

Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase inC. elegans

Meiotic sister chromatid exchanges are rare inC. elegans

C. elegans BRC-1-BRD-1 functions at an early step of DSB processing and inhibits supernumerary crossovers during male meiosis

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