Cell-based chemical fingerprinting identifies telomeres and lamin A as modifiers of DNA damage response in cancer cells
| العنوان: | Cell-based chemical fingerprinting identifies telomeres and lamin A as modifiers of DNA damage response in cancer cells |
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| المؤلفون: | Yukiko Muramatsu, Kazuhiro Tokunaka, Chiaki Fujiwara, Takao Yamori, Hiroyuki Seimiya, Hidetoshi Tahara, Megumi Nishii, Yoshikazu Sugimoto, Masaru Ueno |
| المصدر: | Scientific Reports, Vol 8, Iss 1, Pp 1-15 (2018) Scientific Reports |
| بيانات النشر: | Nature Portfolio, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Telomerase, DNA Repair, DNA repair, DNA damage, Science, Peptide Mapping, Sensitivity and Specificity, Article, Acute Deleterious Effects, 03 medical and health sciences, Cell Line, Tumor, Neoplasms, Humans, Topoisomerase II Inhibitors, Enzyme Inhibitors, Telomere Shortening, Cell Proliferation, Multidisciplinary, Chemistry, Telomerase Activity, Telomere, Lamin Type A, Cell biology, 030104 developmental biology, Cancer cell, Benzamides, Nuclear lamina, Telomerase Inhibition, Medicine, Artificial Cells, Chemical fingerprinting, Hutchinson-Gilford Progeria Syndrome (HGPS), Lamin, DNA Damage |
| الوصف: | Telomere maintenance by telomerase activity supports the infinite growth of cancer cells. MST-312, a synthetic telomerase inhibitor, gradually shortens telomeres at non-acute lethal doses and eventually induces senescence and apoptosis of telomerase-positive cancer cells. Here we report that MST-312 at higher doses works as a dual inhibitor of telomerase and DNA topoisomerase II and exhibits acute anti-proliferative effects on cancer cells and xenografted tumours in vivo. Our cell-based chemical fingerprinting approach revealed that cancer cells with shorter telomeres and lower expression of lamin A, a nuclear architectural protein, exhibited higher sensitivity to the acute deleterious effects of MST-312, accompanied by formation of telomere dysfunction-induced foci and DNA double-strand breaks. Telomere elongation and lamin A overexpression attenuated telomeric and non-telomeric DNA damage, respectively, and both conferred resistance to apoptosis induced by MST-312 and other DNA damaging anticancer agents. These observations suggest that sufficient pools of telomeres and a nuclear lamina component contribute to the cellular robustness against DNA damage induced by therapeutic treatment in human cancer cells. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0834e560c3618cce1ff6a90fe54177db https://doaj.org/article/bcff0d57a37a40e7bac59241a17f8c5f |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0834e560c3618cce1ff6a90fe54177db |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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