Leukemia/lymphoma-related factor (LRF) is a transcriptional repressor characterized by context-dependent key roles in cell fate decision and tumorigenesis.

Researchers demonstrate an unexpected transcription-independent function for LRF in the classical non-homologous end joining (cNHEJ) pathway of double-strand break (DSB) repair.

They find that LRF loss in cell lines and mouse tissues results in defective cNHEJ, genomic instability and hypersensitivity to ionizing radiation.

Mechanistically, authors 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 tumors towards therapeutic treatments based on genotoxic agents or PARP inhibitors following a synthetic lethal strategy.

http://www.nature.com/ncomms/2015/151008/ncomms9325/full/ncomms9325.html