MRNKomplex

The MRN complex, also known as the MRE11-RAD50-NBS1 complex, is a protein assembly that detects DNA double-strand breaks and initiates the cellular response to DNA damage. It comprises three core subunits: MRE11, RAD50, and NBS1 (also called nibrin). In humans, the genes are MRE11, RAD50, and NBN; loss-of-function mutations in NBN cause Nijmegen breakage syndrome.

Upon DNA double-strand breaks, the MRN complex localizes to the break ends, tethers them through RAD50’s coiled-coil regions and zinc-hook motif, and uses the nuclease activities of MRE11 to process DNA ends. It also recruits and activates the ATM kinase, triggering phosphorylation cascades that promote cell-cycle arrest and repair. The MRN complex cooperates with CtIP to initiate end resection, steering repair toward homologous recombination, while it can support non-homologous end joining in certain contexts. Beyond break repair, MRN participates in telomere maintenance and plays a role in meiotic recombination and replication fork stability.

Clinical and biological significance: The MRN complex is highly conserved in eukaryotes and archaea, reflecting its essential role in genome stability. Defects in MRN components lead to genome instability syndromes and affect cancer risk and treatment responses. Nijmegen breakage syndrome arises from NBN mutations, presenting with microcephaly, growth retardation, immunodeficiency, and cancer predisposition. MRE11 mutations can cause ataxia-telangiectasia-like disorder. Together, MRN functions as a central coordinator of DNA damage sensing, signaling, and repair.