Breaking genomic DNA into smaller distinct sizes of fragments is an important step in many sequencing technologies. Current mechanical fragmentation methods, such as sonication, adaptive-focused acoustics or nebulization, generate DNA fragments without base cleavage preferences. These methods, however, have the potential to damage DNA in places other than the phosphodiester bond, and have a lower efficiency of DNA recovery compared to enzymatic methods. On the other hand, enzymatic methods such as those that rely on restriction enzymes with specific recognition sequences produce fragments of a fixed specific size that may be large or small depending on the frequency of the occurrence of the recognition sequences. Thus far, studies on non-specific nucleases have shown that while there are no specific sequences required for recognition and cleavage, these enzymes show a preference for certain bases at the cleavage site (Anderson Nucleic Acids Res. 9(13): 3015-27 (1981); Herrera and Chaires J. Mol. Biol. 236(2): 405-11 (1994)).