A moonlighting nuclease puts CRISPR in its place.

Integration of spacers into CRISPR loci requires the Cas1/Cas2 integrase complex, frequently in combination with Cas4 exonuclease. However, several CRISPR-Cas systems lack Cas4. Whether Cas4-like activity is dispensable in these systems or provided by an unidentified actor was not known. In this issue of the Journal of Biological Chemistry, Ramachandran et al. show that in subtype I-E systems, Cas4-like activity is supplied by DnaQ-superfamily exonucleases, providing a beautiful example of cellular machinery moonlighting in support of CRISPR-Cas adaptive immunity.