Identification and characterization of suppressors of nonhomologous synapsis during «C. elegans» meiosis
Bibliographic record
Abstract
Proper chromosome segregation at meiosis I depends on the initial alignment of homologous chromosomes, the establishment of the synaptonemal complex (SC), and the formation of chiasma between homologs. Previous studies have demonstrated that HIM-3, a component of the meiotic chromosome axis, is required for these processes through the recruitment of the autosomal pairing center proteins (ZIMs) and of SC components like SYP-1. The him-3(vv6) mutation results in the substitution of a highly conserved residue in the HORMA domain, believed to mediate protein-protein interactions. him-3(vv6) mutant germlines display immature and discontinuous axes at early meiosis and the autosomal pairing center (PC) protein ZIM-3 fails to localize properly to the pairing centers, despite the fact that HIM-3vv6 is appropriately expressed and localized; mutants exhibit severe defects in homolog alignment, extensive nonhomologous synapsis and defects in chiasma formation, resulting in a high embryonic lethality (emb) and a high incidence of male (him) phenotype as consequences of chromosome missegregation. To identify proteins that interact with HIM-3 in early meiotic processes and other proteins that function in the HIM-3 pathway, an EMS-based suppressor screen was performed using the vv6 allele and a strong extragenic suppressor, vv39 was isolated. vv39 was identified as a novel allele of cct-4, which encodes the delta subunit of type II chaperonin complex. In wild-type germlines, CCT-4 is localized to the cytoplasm and to the nucleus, indicating that it has a nuclear role. In germlines depleted for cct-4 or other subunits of the CCT complex, axis assembly is delayed, ZIM-3 fails to be recruited to the PCs and SYP-1 fails to localize to the axes, suggesting that the CCT complex is required for morphogenesis of meiotic chromosome axes competent for meiotic processes. In him-3(vv6); cct-4(vv39) mutants, the timely morphogenesis of chromosome axes is appears to be restored and is accompanied by ZIM-3 recruitment to PCs, improved homologue alignment and reduced nonhomologous synapsis. These results collectively suggest that CCT-4 mediates timely axes morphogenesis through CCT-mediated folding of axis component HIM-3 or its interactors. This study is the first to provide insight on the function of molecular chaperonin in mediating meiotic processes and reveals an unprecedented nuclear function for the complex. It would be interesting in the future to further study the nuclear CCT chaperonin complex and its clients to learn more about their roles in meiotic processes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".