Deoxyribonuclease 1 like 3 (DNASE1L3) (DNASE1L3)

Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted endonuclease that plays a pivotal role in the degradation of extracellular DNA, particularly when it is complexed with proteins in the form of chromatin or neutrophil extracellular traps (NETs) (UniProt: P49182; Sisirak et al., 2016, Cell). Unlike its relative DNase 1, DNASE1L3 possesses a unique C-terminal domain that allows it to penetrate and digest lipid-encapsulated or protein-bound DNA, making it essential for the clearance of nuclear debris from dying cells (Keyel, 2017, Dev Biol). Genetic deficiency or functional impairment of DNASE1L3 is a known cause of monogenic systemic lupus erythematosus (SLE) and is associated with the production of anti-dsDNA autoantibodies (Al-Mayouf et al., 2011, Nat Genet). In oncology, DNASE1L3 is frequently downregulated and acts as a tumor suppressor; its absence is linked to increased genomic instability and poor patient outcomes in various cancers (He et al., 2021, Front Oncol). Therapeutic development is primarily focused on enzyme replacement therapy, utilizing recombinant DNASE1L3 or Fc-fusion proteins to restore extracellular DNA clearance in autoimmune and inflammatory disorders (Haj-Ali et al., 2021, J Autoimmun). Additionally, DNASE1L3 activity is being explored as a diagnostic tool, as its absence leads to distinct cell-free DNA fragmentation patterns that can be monitored in liquid biopsies (Serpas et al., 2019, JCI Insight).

Other names

DNase gammaDNAS1L3Deoxyribonuclease I-like 3Liver and spleen DNaseLSDDNase I homolog 2

Enzymatic hydrolysis of extracellular double-stranded DNA, specifically targeting chromatin-bound DNA and neutrophil extracellular traps (NETs) to prevent autoimmune activation and reduce inflammation (Sisirak et al., 2016).