Overview
- A Science study shows that loss of the SPRTN protease allows DNA‑protein crosslinks to accumulate, creating micronuclei and cytosolic DNA that activate the cGAS‑STING innate immune pathway.
- Researchers demonstrate that SPRTN clears crosslinks during both DNA replication and mitosis, and its inactivation triggers interferon‑like inflammatory signaling.
- Mice engineered with an RJALS‑associated SPRTN mutation exhibit strong innate immune activation and progeroid traits, with several abnormalities originating during embryogenesis.
- Pharmacologic or genetic inhibition of cGAS‑STING during development rescued embryonic lethality and alleviated many premature‑aging features, though some defects persisted.
- The findings suggest a potential treatment avenue for DPC‑repair disorders while noting that evidence is confined to cell and mouse models and that DPCs can also arise from environmental exposures such as aldehydes.