LRF maintains genome integrity by regulating the non-homologous end joining pathway of DNA repair

doi:10.1038/ncomms9325

	LRF maintains genome integrity by regulating the non-homologous end joining pathway of DNA repair
	Liu, Xue-Song1,5 ; Chandramouly, Gurushankar 2,6; Rass, Emilie 2; Guan, Yinghua 3; Wang, Guocan 1; Hobbs, Robin M.1; Rajendran, Anbazhagan 2; Xie, Anyong 2,7; Shah, Jagesh V.3; Davis, Anthony J.4; Scully, Ralph 2; Lunardi, Andrea 1,8; Pandolfi, Pier Paolo 1
	2015
发表期刊	NATURE COMMUNICATIONS
ISSN	20411723
EISSN	20411723
卷号	6
发表状态	已发表
DOI	10.1038/ncomms9325
摘要	Leukemia/lymphoma-related factor (LRF) is a POZ/BTB and Krüppel (POK) transcriptional repressor characterized by context-dependent key roles in cell fate decision and tumorigenesis. Here we demonstrate an unexpected transcription-independent function for LRF in the classical non-homologous end joining (cNHEJ) pathway of double-strand break (DSB) repair. We find that LRF loss in cell lines and mouse tissues results in defective cNHEJ, genomic instability and hypersensitivity to ionizing radiation. Mechanistically, we show that LRF binds and stabilizes DNA-PKcs on DSBs, in turn favouring DNA-PK activity. Importantly, LRF loss restores ionizing radiation sensitivity to p53 null cells, making LRF an attractive biomarker to direct p53-null LRF-deficient tumours towards therapeutic treatments based on genotoxic agents or PARP inhibitors following a synthetic lethal strategy. © 2015 Macmillan Publishers Limited. All rights reserved.
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收录类别	EI
出版者	Nature Publishing Group, Houndmills, Basingstoke, Hampshire, RG21 6XS, United Kingdom
EI入藏号	4771365
EI主题词	anatomy - antigen - biomarker - cancer - cells and cell components - DNA - gene expression - genotoxicity - inhibitor - ionization - mutation - protein - rodent - tumor
EI分类号	901 Geobase: Related Topics
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2466
专题	生命科学与技术学院_PI研究组_刘雪松组
共同第一作者	Lunardi, Andrea
通讯作者	Scully, Ralph; Lunardi, Andrea; Pandolfi, Pier Paolo
作者单位	1.Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston; MA, United States; 2.Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston; MA, United States; 3.Department of Systems Biology, Harvard Medical School, 4 Blackfan Circle, HIM 564, Boston; MA, United States; 4.Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Centre, 2201 Inwood Rd, Dallas; TX, United States; 5.School of Life Science and Technology, Shanghai Tech University, Shanghai, China; 6.Fels Institute for Cancer Research and Molecular Biology, Temple University, 3500N. Broad Street, Philadelphia; PA, United States; 7.Sir Run Run Shaw Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; 8.Centre for Integrative Biology (CIBIO), University of Trento, Trento, Italy
第一作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Liu, Xue-Song,Chandramouly, Gurushankar,Rass, Emilie,et al. LRF maintains genome integrity by regulating the non-homologous end joining pathway of DNA repair[J]. NATURE COMMUNICATIONS,2015,6.
APA	Liu, Xue-Song.,Chandramouly, Gurushankar.,Rass, Emilie.,Guan, Yinghua.,Wang, Guocan.,...&Pandolfi, Pier Paolo.(2015).LRF maintains genome integrity by regulating the non-homologous end joining pathway of DNA repair.NATURE COMMUNICATIONS,6.
MLA	Liu, Xue-Song,et al."LRF maintains genome integrity by regulating the non-homologous end joining pathway of DNA repair".NATURE COMMUNICATIONS 6(2015).