@article{7290d0d90fea41bd831fb8220982c4e8,
title = "LRF maintains genome integrity by regulating the non-homologous end joining pathway of DNA repair",
abstract = "Leukemia/lymphoma-related factor (LRF) is a POZ/BTB and Kr{\"u}ppel (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.",
author = "Liu, {Xue Song} and Gurushankar Chandramouly and Emilie Rass and Yinghua Guan and Guocan Wang and Hobbs, {Robin M.} and Anbazhagan Rajendran and Anyong Xie and Shah, {Jagesh V.} and Davis, {Anthony J.} and Ralph Scully and Andrea Lunardi and Pandolfi, {Pier Paolo}",
note = "Funding Information: We are particularly grateful to Dr Fred Alt for his insightful comments and suggestions. We thank current and former members of the Pandolfi laboratory for experimental support and advice. We thank Dr Yufei Xu for assistance in protein complex purification, Dr John Asara for mass-spectrometric analysis, Ms. Shih-Ya Wang for assisting with the laser experiments and data collection, Dr Hong Wang for critical discussion. This work was supported in part by from the National Cancer Institute grants to P.P.P.; by NCI and NIGMS grants to R.S.; by The Giovanni Armenise-Harvard Foundation Career Funding Information: Development Award to A.L.; by a postdoctoral training fellowship from Department of Defense to X.-S.L.; and by a postdoctoral training fellowship from the Susan G. Komen Foundation to E.R. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
month = oct,
day = "8",
doi = "10.1038/ncomms9325",
language = "English (US)",
volume = "6",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}