論文 - 詳細
| RRC ID | 58096 |
|---|---|
| 著者 | Homma H, Nojima H, Kaida A, Miura M. |
| タイトル | Induction of endomitosis-like event in HeLa cells following CHK1 inhibitor treatment. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
The effects of CHK1 inhibitor on cell cycle kinetics have not been fully investigated yet. In this study, we closely analyzed this kinetics using a CHK1 inhibitor (PF00477736) in HeLa cells expressing fluorescent ubiquitination-based cell cycle indicator (Fucci). This system allowed us to visualize cell cycle progression following CHK1 inhibitor treatment in real-time. FACS analysis showed that high levels of DNA damage as determined by γH2AX immunostaining was induced in S phase and that polyploid cells harboring the same levels of DNA damage appeared thereafter. Surprisingly, time-lapse imaging of Fucci fluorescence revealed that many cells entered M phase at once and exhibited prolonged mitosis; eventually progressing to G1 phase not accompanied by cytokinesis; this is an endomitosis-like event. Most of these cells then underwent S/G2 phases at least once, which corroborated the appearance of polyploid cells. However, a small fraction of cells with 2 N DNA content still remained 24 h after the treatment. When co-treated with MAD2 inhibitor, a core factor constituting spindle checkpoint, the 2 N DNA cell fraction disappeared and almost all cells exhibited endomitosis, leading to enhanced sensitivity. Detailed cell cycle analysis revealed that induction of an endomitosis-like event might be associated with CHK1 inhibitor-induced cell death in HeLa cells. |
| 巻・号 | 520(2) |
| ページ | 492-497 |
| 公開日 | 2019-12-3 |
| DOI | 10.1016/j.bbrc.2019.09.046 |
| PII | S0006-291X(19)31767-X |
| PMID | 31610912 |
| MeSH | Benzodiazepinones / pharmacology* Cell Cycle / drug effects Cell Survival Checkpoint Kinase 1 / antagonists & inhibitors* Checkpoint Kinase 1 / metabolism* DNA Damage Fluorescence HeLa Cells Humans M Phase Cell Cycle Checkpoints / drug effects Mad2 Proteins / antagonists & inhibitors Mad2 Proteins / metabolism Mitosis / drug effects* Phosphorylation / drug effects Polyploidy Protein Kinase Inhibitors / pharmacology* Pyrazoles / pharmacology* Time-Lapse Imaging |
| IF | 2.985 |
| 引用数 | 1 |
| 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 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa/Fucci(RCB2812) |