Some embodiments of the methods and compositions provided herein relate to the selective cleavage of a target nucleic acid. Some such embodiments include the selective cleavage of a target nucleic acid that is associated with a DNA-binding protein or comprises a methylated CpG island, with a recombinant nuclease. In some embodiments, the DNA-binding protein comprises a chromatin protein. Some embodiments also include the enrichment of non-target nucleic acids in a sample by selective cleavage of target nucleic acids in the sample, and removal of the cleaved target nucleic acids from the sample.