A method for identifying the presence and position of a single-stranded break within a double-stranded nucleic acid, the method comprising: contacting a sample comprising a double-stranded nucleic acid with DNA polymerase and a nucleotide analog that possesses the ability to base pair with at least two nucleotide bases selected from the group consisting of adenine, guanine, cytosine and thymine, under conditions that allow for DNA polymerase extension and incorporation of the nucleotide analog to occur; contacting the sample with a tagged nucleotide and natural deoxyribonucleotides under conditions that allow for DNA polymerase extension and incorporation of the tagged nucleotide and natural deoxyribonucleotides to occur; fragmenting the double-stranded nucleic acid in the sample, thereby producing a population of double-stranded nucleic acid fragments; isolating double-stranded nucleic acid fragments comprising the tagged nucleotide from the population of double-stranded nucleic acid fragments; ligating an exogenous oligonucleotide sequence to the double-stranded nucleic acid fragments; amplifying the isolated double-stranded nucleic acid fragments comprising the exogenous oligonucleotide sequence, thereby forming an amplified population of isolated double-stranded nucleic acid fragments; identifying the sequence of the amplified population of isolated double-stranded nucleic acid fragments; and within a sequence obtained from the amplified population of isolated double-stranded nucleic acid fragments, identifying a series of three or more consecutive nucleotide positions that have at least two or more detectable nucleotide residues present at a level of at least 10% of all nucleotide residues detected at that position, at each of the three or more consecutive nucleotide positions, thereby identifying the presence and position of a single-stranded break within a double-stranded nucleic acid. contacting a sample comprising a double-stranded nucleic acid with DNA polymerase and a nucleotide analog that possesses the ability to base pair with at least two nucleotide bases selected from the group consisting of adenine, guanine, cytosine and thymine, under conditions that allow for DNA polymerase extension and incorporation of the nucleotide analog to occur; contacting the sample with a tagged nucleotide and natural deoxyribonucleotides under conditions that allow for DNA polymerase extension and incorporation of the tagged nucleotide and natural deoxyribonucleotides to occur; fragmenting the double-stranded nucleic acid in the sample, thereby producing a population of double-stranded nucleic acid fragments; isolating double-stranded nucleic acid fragments comprising the tagged nucleotide from the population of double-stranded nucleic acid fragments; ligating an exogenous oligonucleotide sequence to the double-stranded nucleic acid fragments; amplifying the isolated double-stranded nucleic acid fragments comprising the exogenous oligonucleotide sequence, thereby forming an amplified population of isolated double-stranded nucleic acid fragments; identifying the sequence of the amplified population of isolated double-stranded nucleic acid fragments; and within a sequence obtained from the amplified population of isolated double-stranded nucleic acid fragments, identifying a series of three or more consecutive nucleotide positions that have at least two or more detectable nucleotide residues present at a level of at least 10% of all nucleotide residues detected at that position, at each of the three or more consecutive nucleotide positions, thereby identifying the presence and position of a single-stranded break within a double-stranded nucleic acid.