{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMRE11 is the catalytic core of the MRE11–RAD50–NBS1 (MRN) complex that functions as a primary sensor of DNA double‐strand breaks (DSBs). It collaborates with its partners to recruit and activate key kinases such as ATM and ATR, thereby triggering checkpoint signaling and repair pathways. Although formation of γH2AX foci can occur independently of MRN, the complex is essential for efficient processing of broken DNA ends and the proper assembly of repair foci."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMRE11’s intrinsic endonuclease and exonuclease activities are fundamental for DNA end resection, a process that generates the single‐stranded DNA necessary for commitment to homologous recombination repair. In coordination with regulatory factors such as CtIP, MRE11 directs bidirectional resection that not only facilitates high‐fidelity repair via homologous recombination but also influences the repair pathway choice when alternative nonhomologous end joining is operative."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond DSB sensing and resection, MRE11 plays a pivotal role in maintaining genome stability by safeguarding replication fork integrity and telomere maintenance. Aberrant MRE11 activity contributes to pathological conditions such as ataxia‐telangiectasia–like disorder, mismatch repair–defective cancers, and BRCA2‐associated tumorigenesis. In BRCA2–deficient cells, for example, unrestrained MRE11 nuclease activity leads to replication fork degradation—a process that underlies synthetic lethality with PARP inhibition. 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