Mre11-Rad50-Nbs1 (MRN) protein complex (MRN complex)

The Mre11-Rad50-Nbs1 (MRN) protein complex is a fundamental heterotrimeric assembly central to the cellular DNA damage response [4, 8]. It acts as a primary sensor for DNA double-strand breaks (DSBs), where it tethers broken DNA ends and initiates repair through either homologous recombination or non-homologous end joining [4, 6]. Beyond its structural role, the MRN complex is essential for activating the ATM kinase, which orchestrates downstream checkpoint signaling and cell cycle arrest in response to genetic lesions [1, 2]. Pathogenic mutations in its core components lead to severe genetic syndromes such as Nijmegen breakage syndrome and ataxia-telangiectasia-like disorder, and are increasingly linked to broad cancer predisposition [9, 14]. In oncology, the complex is an emerging therapeutic target; small-molecule inhibitors like Mirin aim to sensitize tumor cells to radiation or poly (ADP-ribose) polymerase (PARP) inhibitors by disrupting essential DNA repair pathways [1, 11]. However, because the complex is vital for maintaining genomic stability in healthy cells, therapeutic strategies targeting this complex must carefully navigate the potential for systemic toxicity and the risk of induced secondary malignancies [1, 14, 16].

Other names

MRE11-RAD50-NBN complexMRE11-RAD50-NBS1 complexMRX complexDNA repair protein complex MRN

Inhibition of MRE11 endonuclease or exonuclease activity, disruption of MRN-dependent ATM kinase activation, and potentiation of synthetic lethality when combined with PARP inhibitors or DNA-damaging agents.