Methods for manipulating biomolecules

A method for preparing a library of at least two nucleic acid fragments of a double stranded nucleic acid, comprising:

• (a) exposing the double stranded nucleic acid to nicking conditions in which, for each strand of the double stranded nucleic acid, at least one linkage between adjacent nucleotides is disrupted at any random location to create a nick while the corresponding nucleotides opposite the nick in the opposing strand of the nucleic acid remain linked wherein the opposing strands remain attached through base pairing interactions, thereby generating a nicked nucleic acid;
• and
• (b) nick translating at least one nick in each strand of the nicked nucleic acid whereby the nick is positioned in sufficiently close proximity to a nick in the opposing strand to generate at least one double-stranded break in the nicked nucleic acid, thereby producing a plurality of nucleic acid fragments of the double stranded nucleic acid, wherein the nicking and/or the nick translating is conducted in the presence of at least one single-strand nucleic acid binding protein, wherein the presence of the at least one single-stranded nucleic acid binding protein improves the yield of fragmented nucleic acids and/or reduces the formation of nucleic acid fragments having rearranged portions;
• and
• (c) ligating the plurality of nucleic acid fragments to adapters.