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, with both endo- and 3' to 5' exonuclease activities, acting on substrates with free single-stranded 3' ends. Double-stranded nucleic acids are not substrates. Activity is higher for DNA than RNA. Templates include R-loops (a bubble-like structure formed when ssRNA replaces one strand in a dsDNA, such as crRNA is thought to form with CRISPR target DNA), circular ssDNA, 2',3'-cAMP and 2',3'-cGMP. Probably generates 3'-phosphate and 5'-hydroxyl ends. In the presence of the Cas3 helicase and ATP dsDNA templates are also degraded. ssDNase activity requires Mg(2+), ssRNase activity does not require cations. A second loosely associated metal ion is visible in the crystal structure. Both ssDNase and ssRNase are inhibited by EDTA. Optimum pH is 7-9, varying somewhat depending on the substrate. 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.