DNASE1L3 maintains homeostatic levels of mitochondrial DNA on the mammalian cell surface.

DNASE1L3 regulates mitochondrial DNA levels on mammalian cell surfaces, preventing autoimmune-related accumulation of surface DNA.

• Why it matters: Understanding how self-DNA is controlled on cell surfaces is crucial for deciphering autoimmune disease mechanisms, as excess surface DNA can trigger immune responses.
• What they did: The study examined mammalian cells, showing mitochondrial DNA tethered by surface proteins and heparan sulfate, with DNA clusters overlapping RNA-binding domains, and tested DNASE1L3's role in clearing surface DNA.
• The result: Findings reveal that DNASE1L3 deficiency leads to increased surface DNA on B and T cells, linking impaired DNA clearance to autoimmune risk, and expanding knowledge of cell surface nucleic acid regulation.