論文 - 詳細
| RRC ID | 88157 |
|---|---|
| 著者 | Oberlitner J, Tinman M, Das A, Koury E, Silva N, Smolikove S. |
| タイトル | Analysis of rad-51 separation of function allele suggests divergence of the synthesis-dependent strand annealing and double Holliday junction pathways prior to RAD-51 filament disassembly. |
| ジャーナル | Genetics |
| Abstract |
DNA double-strand breaks (DSBs) are formed in meiosis, so their repair in the homologous recombination (HR) pathway will lead to crossover formation, which is essential for successful chromosome segregation. HR contains 2 subpathways: synthesis-dependent strand annealing (SDSA) that creates noncrossover and double Holliday junction (dHJ) that generates crossovers. RAD-51 is a protein essential to the formation of all products of HR, as it assembles on the processed DSB, allowing the invasion of the single-stranded DNA into a region of homology. RAD-51 is removed by RAD-54.L after invasion to allow for repair to occur. Here, we investigate a separation of function allele of rad-51, rad-51::FLAG, as compared to 2 other RAD-51 alleles: rad-51::degron and GFP::rad-51. rad-51::FLAG displays slowed repair kinetics, resulting in an accumulation of RAD-51 foci. rad-51::FLAG worms also activate the DSB checkpoint, but to a less extant than that of rad-51 null mutants. In a proximity ligation assay, RAD-54.L and RAD-51 show enriched colocalization in rad-51::FLAG germlines (but not in rad-51::degron), consistent with stalling at the strand invasion step in HR. The defects in RAD-51 disassembly in rad-51::FLAG mutants lead to formation of chromosomal fragments, similar in their magnitude to ones observed in rad-51 or rad-54.L null mutants. However, rad-51::FLAG mutants (unlike a rad-51 null, GFP::rad-51 or rad-54.L null mutants) displayed no defects in the formation of crossover-designated sites (via GFP::COSA-1 localization). Given that rad-51::FLAG worms show checkpoint activation and chromosomal fragments, these results suggest that crossover repair concludes normally, while the noncrossover pathway is perturbed. This is strikingly different from rad-51::degron and GFP::rad-51 strains, which are proficient or deficient in both pathways, respectively. These results suggest that noncrossovers vs crossovers have distinct recombination intermediates and diverge prior to RAD-51 disassembly. |
| 巻・号 | 230(2) |
| 公開日 | 2025-6-4 |
| DOI | 10.1093/genetics/iyaf063 |
| PII | 8107673 |
| PMID | 40192500 |
| PMC | PMC12135186 |
| MeSH | Alleles Animals Caenorhabditis elegans Proteins Crossing Over, Genetic DNA Breaks, Double-Stranded DNA Repair DNA, Cruciform* / genetics DNA, Cruciform* / metabolism Homologous Recombination Meiosis Rad51 Recombinase* / genetics Rad51 Recombinase* / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1524 em2134 |