RAD50 is a core component of the MRN (MRE11-RAD50-NBS1) complex, which functions as a DNA double-strand break (DSB) sensor and repair coordinator 1. The primary role of RAD50 is to bind and hold DNA ends in close proximity while regulating MRE11 nuclease activity through ATP-dependent conformational changes 23. The MRN complex mediates end resection of damaged DNA to generate single-stranded DNA substrates required for homologous recombination repair, an error-free DSB repair mechanism occurring during S and G2 phases 45. Beyond repair, the complex recruits other repair factors and activates ATM and ATR kinases upon DNA damage, independent of MRE11 nuclease activity 46. Recently, RAD50 recruitment has been shown to be potentiated by cGAS interaction, enhancing homologous recombination efficiency 7, and MRE11-RAD50-NBN binding to nucleosomes liberates cGAS for activation during tumorigenesis 8. Regarding disease relevance, germline pathogenic variants in RAD50 show no increased breast cancer risk (odds ratio 0.93) but demonstrate variable cancer predisposition patterns 1. Biallelic RAD50 mutations cause Nijmegen breakage syndrome-like disorder, highlighting its essential role in genome stability maintenance.