Double-strand break repair protein MRE11-DNA repair protein RAD50-Nibrin complex (MRN complex) (MRN complex)

The Double-strand break repair protein MRE11-DNA repair protein RAD50-Nibrin (MRN) complex is a fundamental heterotrimeric assembly essential for the detection and repair of DNA double-strand breaks (DSBs) (UniProt: P49959, Q92817, O60934). It consists of the MRE11 nuclease, the RAD50 ATPase, and the NBN (also known as NBS1 or nibrin) protein, which together coordinate the initial processing of DNA ends for repair via homologous recombination or non-homologous end joining (PubMed: 29307493). Beyond its structural role in tethering DNA ends, the MRN complex acts as a scaffold for the recruitment and activation of the ATM kinase, a master regulator of the DNA damage response and cell cycle checkpoints (PubMed: 18206970). Mutations in the genes encoding these proteins lead to severe genomic instability syndromes, such as Nijmegen breakage syndrome and Ataxia-telangiectasia-like disorder, and are frequently associated with an increased risk of various cancers (NIH: Genetic Home Reference). In the field of oncology, the MRN complex is a significant therapeutic target; its inhibition can sensitize tumor cells to ionizing radiation and DNA-damaging chemotherapeutics (PubMed: 17952061). Small-molecule inhibitors like Mirin and its derivatives are currently being explored in preclinical studies to exploit synthetic lethal vulnerabilities in cancers with specific DNA repair defects (PubMed: 24633280).

Other names

MRE11-RAD50-NBN complexMRE11-RAD50-NBS1 complexMRN complexMRN DNA repair complexMRE11-RAD50-Nibrin complex

Inhibition of MRE11 exonuclease and endonuclease activities, which prevents the processing of DNA double-strand breaks and blocks the recruitment and activation of ATM kinase (PubMed: 17952061, 24633280).