Preprint resolves longstanding debate: C. elegans NUC-1 DNase acts in engulfing cells to clear apoptotic DNA

A preprint posted to bioRxiv characterises the subcellular site of action of NUC-1, a *Caenorhabditis elegans* homologue of mammalian DNase II, during programmed cell death. During embryonic development, cells undergoing apoptosis are engulfed by neighbouring cells and degraded within phagosomes. The fate of the apoptotic cell's chromatin DNA — and which cell type is responsible for its degradation — has been contested in the literature.

Using genetic analysis of *nuc-1* mutant embryos, the authors demonstrate that NUC-1 acts exclusively within engulfing (phagocytic) cells, not within the apoptotic cell itself. In embryos lacking functional NUC-1, apoptotic cell DNA persists undegraded inside phagosomes of the engulfing cell, supporting an exclusively cell-extrinsic mechanism for chromatin clearance.

DNase II homologues are conserved across metazoans, and failure to clear apoptotic DNA is associated with inflammatory and autoimmune phenotypes in mammalian systems. The *C. elegans* findings add mechanistic clarity to a question with broader relevance to understanding how the innate immune system detects and responds to cytoplasmic DNA. This is a preprint and has not yet undergone peer review.