論文 - 詳細
| RRC ID | 76310 |
|---|---|
| 著者 | Trivedi S, Blazícková J, Silva N. |
| タイトル | PARG and BRCA1-BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis. |
| ジャーナル | Nucleic Acids Res |
| Abstract |
Meiotic chromosome segregation relies on programmed DNA double-strand break induction. These are in turn repaired by homologous recombination, generating physical attachments between the parental chromosomes called crossovers. A subset of breaks yields recombinant outcomes, while crossover-independent mechanisms repair the majority of lesions. The balance between different repair pathways is crucial to ensure genome integrity. We show that Caenorhabditis elegans BRC-1/BRCA1-BRD-1/BARD1 and PARG-1/PARG form a complex in vivo, essential for accurate DNA repair in the germline. Simultaneous depletion of BRC-1 and PARG-1 causes synthetic lethality due to reduced crossover formation and impaired break repair, evidenced by hindered RPA-1 removal and presence of aberrant chromatin bodies in diakinesis nuclei, whose formation depends on spo-11 function. These factors undergo a similar yet independent loading in developing oocytes, consistent with operating in different pathways. Abrogation of KU- or Theta-mediated end joining elicits opposite effects in brc-1; parg-1 doubles, suggesting a profound impact in influencing DNA repair pathway choice by BRC-1-PARG-1. Importantly, lack of PARG-1 catalytic activity suppresses untimely accumulation of RAD-51 foci in brc-1 mutants but is only partially required for fertility. Our data show that BRC-1/BRD-1-PARG-1 joint function is essential for genome integrity in meiotic cells by regulating multiple DNA repair pathways. |
| 巻・号 | 50(21) |
| ページ | 12291-12308 |
| 公開日 | 2022-11-28 |
| DOI | 10.1093/nar/gkac1153 |
| PII | 6882108 |
| PMID | 36478097 |
| PMC | PMC9757042 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins* / metabolism DNA Breaks, Double-Stranded DNA Repair* DNA-Binding Proteins* / metabolism GTPase-Activating Proteins* / metabolism Gametogenesis Meiosis |
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オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| 線虫 | tm1524 tm2026 tm1086 |