Single-strand breaks (SSBs) occur when one strand of the DNA double helix experiences breakage of a single nucleotide accompanied by damaged 5’- and/or 3’-termini at this point. One common source of SSBs is due to oxidative attack by physiological reactive oxygen species (ROS) such as hydrogen peroxide. HO causes SSBs three times more frequently than double-strand breaks (DSBs). Alternative methods of SSB acquisition include direct disintegration of the oxidized sugar or through DNA base-excision repair (BER) of damaged bases. Additionally, cellular enzymes may perform erroneous activity leading to SSBs or DSBs by a variety of mechanisms. One such example would be when the cleavage complex formed by DNA topoisomerase 1 (TOP1) relaxes DNA during transcription and replication through the transient formation of a nick. While TOP1 normally reseals this nick shortly after, these cleavage complexes may collide with RNA or DNA polymerases or be proximal to other lesions, leading to TOP1-linked SSBs or TOP1-linked DSBs.