論文 - 詳細
| RRC ID | 65481 |
|---|---|
| 著者 | Kohzaki M, Ootsuyama A, Sun L, Moritake T, Okazaki R. |
| タイトル | Human RECQL4 represses the RAD52-mediated single-strand annealing pathway after ionizing radiation or cisplatin treatment. |
| ジャーナル | Int J Cancer |
| Abstract |
Ionizing radiation (IR) and cisplatin are frequently used cancer treatments, although the mechanisms of error-prone DNA repair-mediated genomic instability after anticancer treatment are not fully clarified yet. RECQL4 mutations mainly in the C-terminal region of the RECQL4 gene lead to the cancer-predisposing Rothmund-Thomson syndrome, but the function of RECQL4ΔC (C-terminus deleted) in error-prone DNA repair remains unclear. We established several RECQL4ΔC cell lines and found that RECQL4ΔC cancer cells, but not RECQL4ΔC nontumorigenic cells, exhibited IR/cisplatin hypersensitivity. Notably, RECQL4ΔC cancer cells presented increased RPA2/RAD52 foci after cancer treatments. RECQL4ΔC HCT116 cells exhibited increased error-prone single-strand annealing (SSA) activity and decreased alternative end-joining activities, suggesting that RECQL4 regulates the DNA repair pathway choice at double-strand breaks. RAD52 depletion by siRNA or RAD52 inhibitors (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside [AICAR], (-)-epigallocatechin [EGC]) or a RAD52-phenylalanine 79 aptamer significantly restrained the growth of RAD52-upregulated RECQL4ΔC HCT116 cells in vitro and in mouse xenografts. Remarkably, compared to single-agent cisplatin or EGC treatment, cisplatin followed by low-concentration EGC had a significant suppressive effect on RECQL4ΔC HCT116 cell growth in vivo. Together, the regimens targeting the RAD52-mediated SSA pathway after anticancer treatment may be applicable for cancer patients with RECQL4 gene mutations. |
| 巻・号 | 146(11) |
| ページ | 3098-3113 |
| 公開日 | 2020-6-1 |
| DOI | 10.1002/ijc.32670 |
| PMID | 31495919 |
| MeSH | Animals Catechin / analogs & derivatives Catechin / pharmacology Cell Line, Tumor Cell Proliferation / drug effects Cisplatin / pharmacology* Cross-Linking Reagents / pharmacology DNA Breaks, Double-Stranded DNA Repair / genetics* HCT116 Cells Humans MCF-7 Cells Mice Mice, Inbred C57BL Mice, Transgenic Neoplasm Transplantation Neoplasms / genetics Neoplasms / pathology Neoplasms / therapy Rad52 DNA Repair and Recombination Protein / antagonists & inhibitors Rad52 DNA Repair and Recombination Protein / genetics Rad52 DNA Repair and Recombination Protein / metabolism* Radiation, Ionizing* RecQ Helicases / genetics* Replication Protein A / genetics Transplantation, Heterologous |
| IF | 5.145 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 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 | HCT116(RCB2979) MCF7(RCB1904) |