Has DNA hydrolytic activity. Is capable of both single- and double-stranded DNA cleavage, producing DNA fragments with 3'-OH ends (PubMed:7957253). Can cleave chromatin to nucleosomal units and cleaves nucleosomal and liposome-coated DNA. Acts in internucleosomal DNA fragmentation (INDF) during apoptosis and necrosis. The role in apoptosis includes myogenic and neuronal differentiation, and BCR-mediated clonal deletion of self-reactive B cells. Is active on chromatin in apoptotic cell-derived membrane-coated microparticles and thus suppresses anti-DNA autoimmunity (By similarity). Together with DNASE1, plays a key role in degrading neutrophil extracellular traps (NETs) (By similarity). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). Degradation of intravascular NETs by DNASE1 and DNASE1L3 is required to prevent formation of clots that obstruct blood vessels and cause organ damage following inflammation (By similarity). Inhibited by zinc. Optimum pH is 7.2. Active from pH 6.0 to 9.0. Monomer. May first pass through the ER membrane before being imported in the nucleus. Contradictory reports exist about the subcellular localization under normal physiological conditions. Under conditions of cell death, may diffuse and/or be actively transported to the nucleus (By similarity). Detected at high levels in spleen, lymph nodes, thymus and liver. Observed also in kidney and testis, but not in brain or heart. Seems to be synthesized as an inactive precursor protein and converted into an active mature enzyme by removal of the N-terminal precursor peptide during apoptosis. Poly-ADP-ribosylated by PARP1. ADP-ribosylation negatively regulates enzymatic activity during apoptosis. Belongs to the DNase I family.