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Splicing function of mitotic regulators links R-loop-mediated DNA damage to tumor cell killing
文献类型：期刊论文
| 作者 | Wan, YH; Zheng, XB; Chen, HY; Guo, YX; Jiang, H; He, XA; Zhu, XL; Zheng, YX |
| 刊名 | JOURNAL OF CELL BIOLOGY
 |
| 出版日期 | 2015 |
| 卷号 | 209期号:2页码:235-246 |
| 通讯作者 | Zheng, YX (reprint author), Carnegie Inst Sci, Dept Embryol, Baltimore, MD 21218 USA.,zheng@ciwemb.edu |
| 英文摘要 | Although studies suggest that perturbing mitotic progression leads to DNA damage and p53 activation, which in turn lead to either cell apoptosis or senescence, it remains unclear how mitotic defects trigger p53 activation. We show that BuGZ and Bub3, which are two mitotic regulators localized in the interphase nucleus, interact with the splicing machinery and are required for pre-mRNA splicing. Similar to inhibition of RNA splicing by pladienolide B, depletion of either BuGZ or Bub3 led to increased formation of RNA DNA hybrids (R-loops), which led to DNA damage and p53 activation in both human tumor cells and primary cells. Thus, R-loop mediated DNA damage and p53 activation offer a mechanistic explanation for apoptosis of cancer cells and senescence of primary cells upon disruption of the dual-function mitotic regulators. This demonstrates the importance of understanding the full range of functions of mitotic regulators to develop antitumor drugs. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | CHROMOSOME ALIGNMENT ; GENOMIC INSTABILITY ; ESCHERICHIA-COLI ; BUB3 STABILITY ; RNASE-H ; P53 ; APOPTOSIS ; PROTEIN ; CANCER ; SPLICEOSOME |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000354012800009 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/14]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Wan, YH,Zheng, XB,Chen, HY,et al. Splicing function of mitotic regulators links R-loop-mediated DNA damage to tumor cell killing[J]. JOURNAL OF CELL BIOLOGY,2015,209(2):235-246. |
| APA | Wan, YH.,Zheng, XB.,Chen, HY.,Guo, YX.,Jiang, H.,...&Zheng, YX.(2015).Splicing function of mitotic regulators links R-loop-mediated DNA damage to tumor cell killing.JOURNAL OF CELL BIOLOGY,209(2),235-246. |
| MLA | Wan, YH,et al."Splicing function of mitotic regulators links R-loop-mediated DNA damage to tumor cell killing".JOURNAL OF CELL BIOLOGY 209.2(2015):235-246. |
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