Splicing function of mitotic regulators links R-loop-mediated DNA damage to tumor cell killing

	Splicing function of mitotic regulators links R-loop-mediated DNA damage to tumor cell killing
	Wan, YH; Zheng, XB; Chen, HY; Guo, YX; Jiang, H; He, XA; Zhu, XL; Zheng, YX
刊名	JOURNAL OF CELL BIOLOGY
	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
内容类型	期刊论文
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.