The telomeric protein TRF2 is critical for the protection of A549 cells from both telomere erosion and DNA double-strand breaks driven by salvicine

doi:10.1124/mol.107.039081

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	The telomeric protein TRF2 is critical for the protection of A549 cells from both telomere erosion and DNA double-strand breaks driven by salvicine
	Zhang, Yong-Wei; Zhang, Zhi-Xiang; Miao, Ze-Hong; Ding, Jian
刊名	MOLECULAR PHARMACOLOGY
	2008-03
卷号	73 期号:3 页码:824-832
ISSN号	0026-895X
DOI	10.1124/mol.107.039081
文献子类	Article
英文摘要	Telomere repeat binding factor 2 (TRF2) has been increasingly recognized to be involved in DNA damage response and telomere maintenance. Our previous report found that salvicine ( SAL), a novel topoisomerase II poison, elicited DNA double-strand breaks and telomere erosion in separate experimental systems. However, it remains to be clarified whether they share a common response to these two events and in particular whether TRF2 is involved in this process. In this study, we found that SAL concurrently induced DNA double-strand breaks, telomeric DNA damage, and telomere erosion in lung carcinoma A549 cells. It was unexpected to find that SAL led to disruption of TRF2, independently of either its transcription or proteasome-mediated degradation. By overexpressing the full-length trf2 gene and transfecting TRF2 small interfering RNAs, we showed that TRF2 protein protected both telomeric and genomic DNA from the SAL-elicited events. It is noteworthy that although both the Ataxia-telangiectasia-mutated (ATM) and the ATM- and Rad3-related (ATR) kinases responded to the SAL-induced DNA damages, only ATR was essential for the telomere erosion. The study also showed that the activated ATR augmented the SAL-triggered TRF2 disruption, whereas TRF2 reduction in turn enhanced ATR function. All of these findings suggest the emerging significance of TRF2 protecting both telomeric DNA and genomic DNA on the one hand and reveal the mutual modulation between ATR and TRF2 in sensing DNA damage signaling during cancer development on the other hand.
WOS关键词	TOPOISOMERASE-II INHIBITOR ; HOMOLOGOUS RECOMBINATION ; DAMAGE RESPONSE ; EARLY EVENT ; IN-VITRO ; ATM ; APOPTOSIS ; KINASE ; LOOP ; PHOSPHORYLATION
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
WOS记录号	WOS:000253444900023
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272967]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Ding, Jian
作者单位	Chinese Acad Sci, Shanghai Inst Matera Med, Div Anti Tumor Pharmacol, State Key Lab Drug Res, Baltimore, MD 21203 USA
推荐引用方式 GB/T 7714	Zhang, Yong-Wei,Zhang, Zhi-Xiang,Miao, Ze-Hong,et al. The telomeric protein TRF2 is critical for the protection of A549 cells from both telomere erosion and DNA double-strand breaks driven by salvicine[J]. MOLECULAR PHARMACOLOGY,2008,73(3):824-832.
APA	Zhang, Yong-Wei,Zhang, Zhi-Xiang,Miao, Ze-Hong,&Ding, Jian.(2008).The telomeric protein TRF2 is critical for the protection of A549 cells from both telomere erosion and DNA double-strand breaks driven by salvicine.MOLECULAR PHARMACOLOGY,73(3),824-832.
MLA	Zhang, Yong-Wei,et al."The telomeric protein TRF2 is critical for the protection of A549 cells from both telomere erosion and DNA double-strand breaks driven by salvicine".MOLECULAR PHARMACOLOGY 73.3(2008):824-832.