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

Xue-Song Liu, Gurushankar Chandramouly, Emilie Rass, Yinghua Guan, Guocan Wang, Robin M. Hobbs, Anbazhagan Rajendran, Anyong Xie, Jagesh V. Shah, Anthony J. Davis, Ralph Scully (), Andrea Lunardi () and Pier Paolo Pandolfi ()
Additional contact information
Xue-Song Liu: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School
Gurushankar Chandramouly: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Centre, Harvard Medical School
Emilie Rass: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Centre, Harvard Medical School
Yinghua Guan: Harvard Medical School
Guocan Wang: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School
Robin M. Hobbs: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School
Anbazhagan Rajendran: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Centre, Harvard Medical School
Anyong Xie: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Centre, Harvard Medical School
Jagesh V. Shah: Harvard Medical School
Anthony J. Davis: University of Texas Southwestern Medical Centre
Ralph Scully: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Centre, Harvard Medical School
Andrea Lunardi: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School
Pier Paolo Pandolfi: Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: Abstract 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.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms9325 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9325

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9325

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().