CRISPR (clustered regularly interspaced short palindromic repeat), is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). Cas3 plus Cascade participate in CRISPR interference, the third stage of CRISPR immunity. Acts as a ssDNA and ssRNA nuclease, probably with both exo- and endonuclease activities. Activity is higher for DNA than RNA. Templates include 2',3'-cAMP and 2',3'-cGMP. ssDNase activity requires Mg(2+), ssRNase activity does not require cations. Both ssDNase and ssRNase are inhibited by EDTA. Optimum pH is 7-8. Monomer. Proteins of this family have an N-terminal nuclease domain and a C-terminal helicase/ATPase domain. In some CRISPR/Cas systems the domains are swapped, in others they are encoded separately. Belongs to the CRISPR-associated nuclease Cas3-HD family.