論文 - 詳細
| RRC ID | 46444 |
|---|---|
| 著者 | Silva N, Adamo A, Santonicola P, Martinez-Perez E, La Volpe A. |
| タイトル | Pro-crossover factors regulate damage-dependent apoptosis in the Caenorhabditis elegans germ line. |
| ジャーナル | Cell Death Differ |
| Abstract |
During meiosis, DNA double-strand breaks (DSBs) are physiologically induced to start the recombination process and promote the formation of interhomologue crossovers (COs), which are required to ensure faithful chromosome segregation into the gametes. The timely repair of DSBs is an essential part of the meiotic programme, as accumulation of unprocessed DSBs during the pachytene stage of meiotic prophase triggers a DNA damage checkpoint response that induces apoptosis of damaged cells. We show that CO-promoting factors MSH-4, MSH-5, and ZHP-3, but not COSA-1, are required for the apoptotic response of the meiotic DNA damage checkpoint. Lack of MSH-4 or MSH-5 suppresses the apoptotic response observed in some DNA repair-defective mutants such as fcd-2 and brc-1 (orthologues of FANCD2 and BRCA1), irrespectively of the amount of DSBs present in pachytene nuclei. Although ionizing radiation fails to induce apoptosis in msh-4/5-mutant backgrounds, it induces transcriptional activation of the apoptosis-activator egl-1, which is controlled by the Caenorhabditis elegans p53 orthologue CEP-1. This finding suggests that MSH-4/5 involvement in the apoptotic response occurs downstream or independently of damage sensing and checkpoint activation. This study establishes a role for pro-CO factors MSH-4/5 and ZHP-3 in the execution of apoptosis at late meiotic prophase following the accumulation of exogenous or endogenous DNA damage. |
| 巻・号 | 20(9) |
| ページ | 1209-18 |
| 公開日 | 2013-9-1 |
| DOI | 10.1038/cdd.2013.68 |
| PII | cdd201368 |
| PMID | 23832114 |
| PMC | PMC3741503 |
| MeSH | Animals Apoptosis / genetics* Apoptosis / radiation effects Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism* DNA Breaks, Double-Stranded DNA Repair / genetics* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Meiosis / genetics Radiation, Ionizing Repressor Proteins / genetics Repressor Proteins / metabolism Transcriptional Activation / radiation effects Tumor Suppressor Protein p53 / metabolism |
| IF | 10.717 |
| 引用数 | 7 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| 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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| 各媒体での言及数の合計 | 0 |
| 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 | tm3298 tm1145 tm1298 |