DNA2 is a multifunctional enzyme essential for DNA replication and repair in both nuclear and mitochondrial compartments. Functionally, DNA2 processes Okazaki fragments by cleaving long DNA-RNA primer flaps (>27 nucleotides) that escape FEN1 processing, converting them into substrates for FEN1 completion 1. The enzyme possesses ssDNA-dependent ATPase, 5'-3' helicase, and endonuclease activities, with the nuclease and ATPase functions being critical for its primary roles 1. DNA2 is recruited by BLM to mediate 5' single-stranded DNA end resection during double-strand break repair, a process that commits cells to homology-dependent repair pathways 23. The BLM-DNA2 nuclease complex functions in long-range resection following MRE11-catalyzed short-range resection 3. Clinically, DNA2 mutations cause mitochondrial DNA maintenance defects (MDMDs), characterized by impaired mtDNA synthesis leading to deletions and depletion, resulting in energy production insufficiency in affected tissues 4. Known disease associations include progressive external ophthalmoplegia with mtDNA deletions, Rothmund-Thomson syndrome, and Seckel syndrome. DNA2's regulatory role in DNA replication checkpoints independent of Okazaki fragment processing suggests broader genome integrity functions requiring further investigation.