論文 - 詳細
| RRC ID | 50090 |
|---|---|
| 著者 | Fujimoto M, Takii R, Takaki E, Katiyar A, Nakato R, Shirahige K, Nakai A. |
| タイトル | The HSF1-PARP13-PARP1 complex facilitates DNA repair and promotes mammary tumorigenesis. |
| ジャーナル | Nat Commun |
| Abstract |
Poly(ADP-ribose) polymerase 1 (PARP1) is involved in DNA repair, chromatin structure, and transcription. However, the mechanisms that regulate PARP1 distribution on DNA are poorly understood. Here, we show that heat shock transcription factor 1 (HSF1) recruits PARP1 through the scaffold protein PARP13. In response to DNA damage, activated and auto-poly-ADP-ribosylated PARP1 dissociates from HSF1-PARP13, and redistributes to DNA lesions and DNA damage-inducible gene loci. Histone deacetylase 1 maintains PARP1 in the ternary complex by inactivating PARP1 through deacetylation. Blocking ternary complex formation impairs redistribution of PARP1 during DNA damage, which reduces gene expression and DNA repair. Furthermore, ternary complex formation and PARP1 redistribution protect cells from DNA damage by promoting DNA repair, and support growth of BRCA1-null mammary tumors, which are sensitive to PARP inhibitors. Our findings identify HSF1 as a regulator of genome integrity and define this function as a guarding mechanism for a specific type of mammary tumorigenesis. |
| 巻・号 | 8(1) |
| ページ | 1638 |
| 公開日 | 2017-11-21 |
| DOI | 10.1038/s41467-017-01807-7 |
| PII | 10.1038/s41467-017-01807-7 |
| PMID | 29158484 |
| PMC | PMC5696371 |
| MeSH | Animals BRCA1 Protein / genetics BRCA1 Protein / metabolism Breast Neoplasms / genetics* Breast Neoplasms / metabolism* Breast Neoplasms / pathology Carcinogenesis / genetics Carcinogenesis / metabolism* DNA Damage DNA Repair* Female Genomic Instability Heat Shock Transcription Factors / genetics Heat Shock Transcription Factors / metabolism* Humans Mice Poly (ADP-Ribose) Polymerase-1 / genetics Poly (ADP-Ribose) Polymerase-1 / metabolism* Protein Binding RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism* |
| IF | 12.121 |
| 引用数 | 18 |
| 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 | X(Twitter) |
| 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 | |
| ヒト・動物細胞 | MCF7(RCB1904) |