論文 - 詳細
| RRC ID | 65848 |
|---|---|
| 著者 | Koike M, Yutoku Y, Koike A. |
| タイトル | Cloning, localization and focus formation at DNA damage sites of canine Ku70. |
| ジャーナル | J Vet Med Sci |
| Abstract |
Understanding the molecular mechanisms of DNA double-strand break (DSB) repair machinery, specifically non-homologous DNA-end joining (NHEJ), is crucial for developing next-generation radiotherapies and common chemotherapeutics for human and animal cancers. The localization, protein-protein interactions and post-translational modifications of core NHEJ factors, might play vital roles for regulation of NHEJ activity. The human Ku heterodimer (Ku70/Ku80) is a core NHEJ factor in the NHEJ pathway and is involved in sensing of DSBs. Companion animals, such as canines, have been proposed to be an excellent model for cancer research, including development of chemotherapeutics. However, the post-translational modifications, localization and complex formation of canine Ku70 have not been clarified. Here, we show that canine Ku70 localizes in the nuclei of interphase cells and that it is recruited quickly at laser-microirradiated DSB sites. Structurally, two DNA-PK phosphorylation sites (S6 and S51), an ubiquitination site (K114), two canonical sumoylation consensus motifs, a CDK phosphorylation motif, and a nuclear localization signal (NLS) in the human Ku70 are evolutionarily conserved in canine and mouse species, while the acetylation sites in human Ku70 are partially conserved. Intriguingly, the primary candidate nucleophile (K31) required for 5'dRP/AP lyase activity of human and mouse Ku70 is not conserved in canines, suggesting that canine Ku does not possess this activity. Our findings provide insights into the molecular mechanisms of Ku-dependent NHEJ in a canine model and form a platform for the development of next-generation common chemotherapeutics for human and animal cancers. |
| 巻・号 | 79(3) |
| ページ | 554-561 |
| 公開日 | 2017-3-23 |
| DOI | 10.1292/jvms.16-0649 |
| PMID | 28163277 |
| PMC | PMC5383176 |
| MeSH | Active Transport, Cell Nucleus Amino Acid Sequence Animals Base Sequence Cell Line, Tumor Cell Nucleus / metabolism Conserved Sequence DNA Breaks, Double-Stranded DNA Damage* DNA End-Joining Repair DNA Repair Dogs Humans Ku Autoantigen / genetics Ku Autoantigen / metabolism* Lasers Mice Protein Processing, Post-Translational |
| IF | 1.049 |
| 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 | HeLa HCT116(RCB2979) |