MRE11 is a critical DNA repair nuclease that forms the MRN complex with RAD50 and NBN, serving as a primary sensor and processor of DNA double-strand breaks 1. The protein exhibits 3'-5' exonuclease activity and binds both single-stranded and double-stranded DNA to initiate homologous recombination repair through DNA end resection 12. MRE11 function is regulated through multiple post-translational modifications: UFMylation at K282 promotes MRN complex formation and optimal ATM activation 3, while lactylation at K673 enhances DNA binding and facilitates DNA end resection 4. Beyond DNA repair, MRE11 plays crucial roles in tumor suppression by liberating cGAS from nucleosome sequestration, enabling cGAS-STING pathway activation and promoting necroptosis in response to oncogenic stress 5. The protein also coordinates replication stress responses with interferon signaling during oncogene-induced senescence 6. Clinically, germline pathogenic variants in MRE11 show limited association with increased cancer risk, unlike variants in NBN which significantly increase melanoma, pancreatic, and hematological cancer risks 7. MRE11's central role in maintaining genome stability makes it a potential therapeutic target, particularly in BRCA1/2-deficient cancers where it mediates replication fork degradation 8.